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TR N G I HC
Dc
H N I
***********
L TH NGA
T T N G H I P DU c S K H A 2 0 0 3 -2 0 0 8 )
: B m n D c l
Trng i h c D c H N i
Thi gian thc hin: 022008 - 05/2008
V
I A V ^L.
hi cm 0R
B c kt' qu bo co nh ngy hm nay, ti xin by lng bit
1 su s c ti T I. S o Thi Vui - Rg thy n tnh du dt v
hng dn ti hon thnh Kha lun ny.
Ti xin chn hnh cm n c c thy c gio trong B mn Bc l
to mi iu hin v nhit tinh gip li trong sut thi gian hc
tp v lm Kha lun.
T Hi. ngy 2 1 /0 5 /2 0 0 8
Sinh vin: li Th ga
MC LC
T VN ......................................................................................................................... 1
1. V I M V T H U C C H N G V I M ........................................................................ 2
1.1. T CNG V V I M .............................................................................................2
1.1.1. Khi n i m .............................................................................................................. 2
1.1.2. Nguycn nhn gy v ic m .....................................................................................2
1.1.3. Phn l o i .................................................................................................................2
1. .4. Din bin phn ng viin ................................................................................. 3
1.1.5. Cc yu t tham gia vo phn ng v ic m ....................................................5
1.2. T H U C C H N G V I M ....................................................................................... 1 ]
1.2.1. Ha dc chng v ic m ...................................................................................
1.2.2. ng dc chng vim ................................................................................ 14
2.2. M hnh gy
vim mn t n h ...............................................................................2 6
4. KT LUN V XUT.......................................................................... 45
4.1. Kt l u n .......................................................................................................................... 4 5
4.2. xut.............................................................................................................................4 6
T I L I U TH A M KH O
PH U L C
CH THCH CC T VIT TT
C O X -1
C y c lo o x y g c n a sc -1
C O X -2
C yclooxygenase-2
DM SO
Dimethyl Sulfoxid
FM LP
IL -]
Incrlcukin-1
IL -6
Interleukin-6
IL -8
Inlerleukin-8
LOX
Lipooxygcnasc
LPS
LTB4
N SA ID s
Lipopolysaccharid
Lcucotrien B4
Non-Stcroidal Anti-Inriammalory Drugs Thuc chng vim
khng steroid
PAF
PG
Prostaglandin
P G Ej
Prostaglandin E|
PCi E 2
Prostaglandin E 2
PGE3
Prostagiandin E,
P G I2
Prostacyclin
TNF
TXA2
Thromboxan A ,
T VN
Vim l mt hin tng bnh l ph hin, theo thng k c 1/3 bnh nhn n
khm hay nhp vin l c tnh trng vim. Ngy nay, nh s pht trin ca y dc
hc, con ngi c nhng hiu bit su hn v c ch phn t ca phn ng vim.
T gip tm ra cc c ch tc dng ca thuc chng vim, ng thi gi ra nhng
hng mi trong nghin cu pht trin ihuc chng vim mi. Hin nay c nhiu
thuc chng vim c s dng nh NSAIDs. glucocorticoid, enzym chng vim,
dc liu chng vim, trong NSAIDs v glucocorticoid l hai nhm thuc chng
vim kinh in, c tc dng tt trn nhiu loi vicm v c s dng ph bin.
Nhng cc thuc ny cng c nhiu lc dng khng mong mun: gy vim lot
ng tiu ha, nh hng qu trnh ng mu, to mu, xp xng...gy nguy
him cho cc bnh nhn c bit l vi cc bnh nhn vim mn tnh. V vy, vic
tm kim, nghin cu cc thuc chng vim mi c hiu qu tt. t tc dng khng
mong mun l yu cu cp thit i vi cc nh khoa hc. T lc pht hin ra ti m
nng ca mt dc liu cng nh ha dc chng vim n lc bin n tr thnh
mt ch phm thuc hon chnh l c mt chng ng di, trong giai on tin
lm sng-th tc dng dc l l khu rt quan trng. V thc hin vic th
khng th thiu cc m hnh thc nghim ph hp gip chng minh thuc thc
s c tc dng hay khng? liu lng trong khong no? c ch tc dng ra sao?
Hin nay ti Vit Nam cc m hnh nghin cu tc (lng chng vim ca
thuc cn t v hn ch cng nh cha c thng kc mt cch y . V vy
chng ti tin hnh thc hin ti "Tng quan v cc m hnh nghin cu tc
dng chng vim ca thuc" vi mc tiu:
+ Tng quan v cc m hnh nghin cu tc dng chng vim ca thuc.
+ nh gi cc m hnh nghin cu tc dng chng vicm ca thuc.
+ Bc u la chn mt s m hnh nghin cu tc dng chng vi m ca
thuc ph hp vi iu kin thc t Vit Nam.
o thuc...
-D o yu t vt l: chn thng, d vt, nhit (hng nng, hng lnh), tia phng
x. bc x...
Nguyn nhn ni sinh
- Sn phm chuyn ha: nh ur mu tng gy vim mng phi, mng lim;
aicd uric tng gy vim khp trong bnh Gt.
- H oi t kn gy vim v trng: nh hoi t chm xng i.
- Phn ng t min-, nh bnh thp khp, vim cu thn.
- Vim xung quanh t chc ung th ...
1.1.3. Phn loi
- Theo nguyn nhn: vim nhim trng v vim v trng.
- Theo v tr: vim nng, vim su hoc vim bn ngoi, vim bn trong.
- Theo dch r vim: vim Ihanh dch, vim t huyt, vim mu...ty theo dch r
vim ging huyt thanh, huyt tng hay cha nhiu bch cu thoi ha.
Lympho bo B: tham gia vo min dch dch th. Khi khng nguyn vo c
th s gn vi t bo B c khng thd b mt tng ng ri kch thch bit ha t bo
B thnh tng bo c kh nng sn xut khng th (IgE, IgG, IgA, IgD, IgM).
Prostaglandin
Khi t bo b tn thng, mng pho.spholipid ca l bo s b hot ha bi
phospholipase A2 to ihnh acid araehidonic. Prostaglandin l sn phm chuyn ha
ca acid arachidonic theo con ng cyclooxygenase (C O X ). C hai loi cnzym
c o x ng phn l COX-1 v COX-2. C O X -1 l en/ym c mt hu ht cc m,
chu trch nhim tng hp prostaglandin sinh tham gia vo cc chc nng bnh
thng ca mt s c quan trong c Ihc (c bit ng tiu ha, tiu cu v thn),
n nh ni m v bo v t' bo. C O X -2 c xcm l enzym tin vicm, ch xut
hin ti cc t chc b tn thng v c vai tr to ra cc prostaglandin gy vim.
Bnh Ihng nng COX-2 trong t bo rt thp. Trong cc m vim, kch thch
vim gy cm ng cc t bo tham gia vo phn ng vim (bch cu n nhn, i
thc bo, t bo ni m c...) t hot ha mnh COX-2 v nng COX-2 c th
tng cao gp 80 ln bnh thng.[ 13,20]
Trong vim cp, cc m v mch mu ti ch sn xut PGE, v PGI2. Trong vicm
mn, cc bch cu n nhn v i thc bo gii phng PGE, v T X A 2.
[9J.
Cc acid amin hot mch
Histamin
Ngun gc: histamin c ngun gc ch yu t dng bo, ngoi ra cn c
trong bch cu i kim v tiu cu. N c to thnh v d tr Irong cc ht ca
cc t bo ny. Histamin c gii phng do qu trnh mt hl ca cc t ho khi
p ng vi cc kch thch.[9, 13]
Vai tr trong vim: histamin gy gin tiu ng mch v c coi l cht trung
gian chnh trong giai on khi u tng tnh thm thnh mch. N gv co cc t
bo ni mc ca tiu tnh mch, gin rng vng ni gia cc t bo ny v cho huyt
tng thm qua vo ni m.[5. 13]
Serototiin
Ngun gc: serotonn c ngun gc t tiu cu v cc t ho a crom rut.
S kt dnh tiu cu s gii phng serotonin. 13)
Vai tr Irong vim: lng t histamin.
Yu t hot ha tiu cu (PA F)
PAF c hnh thnh trong mng cc tiu cu. t bo ni m. hch cu a
nhn trung tnh (sau khi b kch thch), bch cu i toan, t bo cn nhn, t bo li
v cu thn t mt loi phospholipid nh phospholipase A2.
Tc dng ca PAF l hot ha bch cu a nhn trung lnh nhm kch thch
chng bm dnh vo t ho ni m. PAF cng gv v ht, m u cho vic tit cc
enzym Iv gii v gii phng superoxyd. Mt tc dng khc l lm tng tnh thm
thnh mch, gy ph. Ngoi ra n c tc dng co tht phc' qun lm cho cn hen
nng hn v cng tc dng ln cc t bo mu (gim bch cu, gim tiu cu) [9J.
huyt qun v gy gin mch, lng tnh (hm Ihnh mch, tng sn xul cc PG
vicm. Ngoi ra NO cn lm gim t lp v kl dnh tiu cu.
NO do i thc bo sn xut s tc ng nh cc gc t do l yu t c vi t
bo vi khun, nm, virus, t bo u. Tuv nhin, nu cc i thc bo b hot ha sn
xut qu nhiu NO s gy hi cho c th nh gin mch nng v chong trong sc
nhim khun [13].
C c cht trung gian c ngun gc huyt tng /5 , 7]
Bao gm: h thng b th, h thng ng mu, h thng tiu t huyt, h
thng kinin v cc globulin min dch. Trong 4 h thng u licn c to thnh
theo kiu dng thc v c mi tng quan ln nhau.
H thng b th
Vai tr: dit khun nh cc thnh phn cui ca h thng b th; gia tng phn
ng vicm nh cc sn phm ph nh C3a, C5a khi hot ha t C1 n C5 bao gm
s opsonin ha. ha hng ng bch cu, thot ht t bo mast.
H thng ng mu
Vai tr: ngn s pht tn ca vi khun; gi vi khun v vt l ni m hot
ng thc bo mnh nht; lo thnh b khung to iu kin cho s sa cha v lnh
vt thng.
H thng kinin
Kinin cn bn l bradykinin, c vai tr: gy gin mch: cng tc ng vi PCi
gy au; gy co Iht c trn ngoi mch mu; gy tng tnh thm thnh mch do
cng tc ng vi PG nhm E trong giai on sau ca qu trnh vim: tng ha ng
ng bch cu.
H thng tiu
t huyt
10
1.2.
C ch chng vim
NSAIDs gn vo v tr hot ng dnh cho acid arachidonic trn c o x gy c
ch cnzym c o x lm cho aci arachidonic khng chuyn thnh prostagandin- cht
trung gian ha hc gy vim nn NSADs c ch phn ng vim (hnh I ).
Ngoi ra NSAIDs c ch h enzym phn hy proiein trong lysosom, lm vng
bn mng lysosom v i khng tc dng ca cc cht trung gian ha hc nh
bradykinin. histamin, serotonin. c ch ha hirng ng bch cu, c ch s di
chuyn ca bch cu ti vim.
C h nh chung
Chng vim: c vim cp v mn (vim khp dng ihp, thp khp, vim ct
sng dnh khp, hnh gt...)
Ngoi ra thuc cn dng gim au v h st.
1.2.1.2. Thuc chng vim steroid [4, 8]
Thuc chng vim steroid cn gi l cc glucocorticoid, bao gm mt s
thuc: hydrocortison, prednisolon, methylprcdnisolon, triamcinolon. dcxamcthason,
betamethason...
12
C ch chng vim
Glucocorticoid c ch phospholipase A2 thng qua kch thch tng hp
lipocortin lm gim tng hp acid arachidonic. do lm gim tng hp leucotrien
v prostaglandin, v vy c ch phn ng vim.
Ngoi ra n cn c tc dng c ch dng bch cu n nhn, trung tnh,
lympho bo i vo m gy khi phi phn ng vim.
C h nh
iu tr vicm khp, vim da. vim c...
Ngoi ra cn dng iu tr Ihay th hormon trong suy thng thn, iu tr cc
bnh t min, ng, sc phn v...
1.2.1.3. Enzvm chng vim
Bao gm mt s cnzym: a-chymotrypsin. trypsin, serratiopeptidase. amylase.
papain, bromelain.
C ch chng vim
Thy phn protein huyt tng, tiu hy mnh vn si to keo, cc mnh t
bo v cc fibrin kt t ti vng b tn thng ng thi kch thch hin tng thc
bo. V vy chng lm gim ph vim, ci thin kh nng lu Ihng ca mu. phc
hi lun hon mao mch m ho cung cp oxv V1 dinh dng cho cc vng
b tn thng.
iu ha cc cht trung gian ha hc ca vim nh cc protein ca pha cp,
cc cytokin. cc th th gy kt dnh trn mng bch cu.
c ch cc protcase. cc protcin thu dn gc t do.
Gim kh nng hot ha h thng b (h ca phc hp min dch mng t ho,
lm gim s nguy him ca cc phn ng qu mn [13].
13
C h nh
Chng vim, chng ph n sau phu thut, chn thng, trong tit niu, sn
ph khoa, tai mi hng.
1.2.2. ng dc chng vim
Theo quan im ca ng y, vim l triu chng ca c th khi b nhim c.
Nguvn nhn nhim c c the do bn trong (ph tng hot ng yu, khng sc
thanh thi cht c) hoc do bn ngoi (cn trng cn. hi ha cht, ng c thc
n...)* V th. trong ng y cc v thuc chng vim thng l cc Ihuc thanh, tiu
v hot nh thuc ihanh nhit gii c, thuc tr thp, thuc hot huvt tiu ...
C rt nhiu dc liu v bi thuc c truyn c tc dng chng vim c
s dng rng ri trong dn gian v hin nay ang c nghin cu tm ra cc
hot cht c kh nng chng vim cng nh c ch chng vim ca cc hot cht
.
Mt s dc liu chng vim [2, 3]
Kim ngn
Tn khoa hc: U m icera aponica Thunb. Capritbliaccae
B phn dng: hoa, phn trn ml l phi hay sy kh
Cng dng: Kim ngn hoa c dng ch yu cha mn nhl, mn nga,
st nng, st rt, t l v vim nhim trng ng h hp trn, vim da, vim mng
kt do sicu vi...
H e hoa
Tn khoa hc: Sophora aponica L. Fabaceac.
B phn dng: n hoa hc
Cng dng: ch yu phng nhng bin c ca bnh x va ng mch, iu
tr cc trng hp suy yu tnh mch, cc Irng hp xut huyt nh chy mu cam,
ho ra mu, t cung xut huyt, cc trng hp tn thng ngoi ra do bc x, chng
d ng. thp khp, lm vt thng chng lnh so.
Nc nc
Tn khoa hc: Oroxyum imicum Bignoniaceae.
B phn dng: v thn v ht phi hay sy kh.
14
Ngn kiu tn
Thnh phn:
Trc dip
Lin kiu
Kinh gii
m u x
Thng ma
Ngu bng t
Ct cnh
Bc h
Cam tho
T mc
Ngi cu
L mng tay
Ngh vng
Huyt gic
Ch tr: cm cm, mn nhl
c hot
T tn
Thc a
Phc linh
Tang k sinh
ng quy
trng
Cam tho
Tn giao
Thc dc
Ngu tt
u tm
Phng phong
Xuvn khung
Nhn sm
15
2.
vim, triu chng lm sng ca vim, ngi ta to ra cc m hnh vicm thc nghim
dng nghin cu tc dng chng vim ca thuc. Cc m hnh ny c the chia
thnh 3 loi:
- M hnh gy vim cp v bn cp
- M hnh gy vicm mn tnh
- M hnh nghin cu c ch chng vicm
2.1.
M HNH G Y V IM C P V BN C P
Vim c th do nhiu nguyn nhn gy ra nh nhim khun, thiu mu cc b,
Nguyn tc
M hnh ny c th dng nhiu cht gv vim khc nhau nh carrageenin,
dextran. kaolin. formaldehy. men bia, albumin trng...Khi tim cc cht ny vo
bn chn chut s kch thch gii phng cc cht trung gian ha hc nh histamin.
prostaglandin, serotonin...v kt qu l gy ph. Thuc c kh nng c ch ph bn
chn chut c coi l c tc dng chng vicm.
2.1.1.1. (y ph chn chut bng carrageenin [29]
Tin hnh
S dng chut cng c 2 ging, trng lng khong 100-150 g. chia ngu
nhin thnh cc l:
16
nh gi
T l % tng th tch bn chn ca mi chut biu th mc vim cp c
tnh theo cng thc (1):
V -V
X % = ~ L ------ X 100
y
o
tu
Trong :
Y % - Vt%
% = C 1 Xt
0/
X 100(2)
v 7
Trong :
khc nh: hn dch kaolin 5%; dung dch lng trng trng 1%; formalin 1% (Turner
1965); dextran 1% n 3% (Turner 1965); dextran 6% (Winter, 1963); dung dch
carrageenin % thm 00 ri PGE2 hoc PG, hn dch bt men bia 2,5% : 0,1 ml
dung dch trvpsin 0,1% : dung dch coagenase ; dung dch serotonin 0,02%;
Nguyn tc
Khi tc ng lc c hc mnh ln bn chn chut s gy tn thirng m v t
bo chn chut, lm hot ha phospholipase A7 gy gii phng acid arachidonic l
phospholipid mng. Acid arachidonic s chuyn ha thnh prostaglandin nhen/ym
c o x v kt qu l gy ph. M hnh ny m phng tnh trng tng t trn lm
sng khi c th b chn thng nh bong gn, ng, va p...
Tin hnh
S dng chut cng trng, chut c chia ngu nhin thnh cc l:
L chng: ung dung dch nc mui sinh l
L i chiu: ung thuc chng vim bit
L th: ung thuc ang nghin cu tc dng chng vim
Cho chut ung thuc hoc nc mui sinh l vo mi bui sng trong 4 ngy
lin tc. n ngy th 5. sau khi cho chut ung thuc hoc nc mui ln cui 1
gi th gy vim bng cch th 1 qu nng 100 g t cao 50 cm xung bn chn
chut. o thc lch bn chn chut ti cc thi im: trc khi gy vim, sau khi gy
vim 1, 3, 5 gi [18].
nh gi
Tnh t l % tng th tch chn chut, ri tnh t l % c ch ph ca l th
so vi l chng theo cng thc (1) v (2) tng t nh mc 2.1.1.1.
2.1.2. M hnh gv ph tai chu
2.1.2.1. Gy ph tai chut bng oxazolon [29]
18
Nguyn tc
M hnh gy ph tai chut hng oxazolon do Evans gii thiu ln u tin nm
1971. y l m hnh da trn phn ng qu mn chm ca c th vi oxazo1on. kt
qu l kch thch lm v ht t bo mast, gii phng cc cht trung gian gy ph.
Tin hnh
S dng chut nht c 2 ging, trng lng Irung bnh khong 25 g, chia ngu
nhin thnh cc l:
L chng: bi 0,01 ml oxa?,olon 2% trong accton
L i chiu: bi 0 . 0 1 ml oxazolon 2% trong aceton d ha tan thuc
chng vim bit ( hydrocortison 0.03% hoc indomethacin 1%)
L th: hi 0,01 ml oxazolon 2% trong aceton ha tan thuc ang
nghin cu.
Gy m chut hng halothan. Bi 0 J ml oxazolon ln vng da bng co
lng hoc bi 0,01 ml oxazolon ln phn trong ca c 2 tai chut lm chut nhy
cm vi cht kch thch oxazolon. Sau 8 ngy, gy m chut ri kch thch gy
vimbng cch bi ln pha trong
nh gi
Tnh t l % lng khi lng ca tai phi so vi tai tri ri tnh gi tr trung
bnh t l % tng khi lng tai chut trong mi l. Sau tnh t l % c ch ph
ca l th so vi l chng. Cng thc tnh tng t mc 2 .1 .1 .1.
19
Nguyn tc
M hnh gy ph tai chut hng du ba u do Tonelli v cng s xul
(1965) dng nh gi ng thi tc dng chng vim v tc dng tco tuyn
Tin hnh
Th nghim c th thc hin trn chut nht c trng lng 22 g hoc chut
cng c trng lng 70g. chut c chia ngu nhin thnh cc l:
L chng: dng dung mi pha thuc
L i chiu: dng thuc chng vim bit.
L th: dng thuc ang nghin cu tc dng chng vim.
Chun b hn hp dung mi gm c du ba u: ethanol: pyridine: ethyl ether
(t l 1:10:20:69 chut nht v 4 :10 :20 :6 6 chut cng). Thuc di chiu v thuc
th dc ha tan trong dung mi ny vi nng 0,03 n 1 mg/ml nu th nghim
trn chut nht v nng cao hn t 3 n 10 ln nu th nghim trcn chut cng.
Gy m chut ri bi ln c 2 mt ca tai phi cc dung dch tng ng cho
mi l (0,01 ml vi chut nht v 0,02 ml vi chut cng). Tt c cc tai tri c
gi nguyn. Sau 4 gi, git chut hng thuc m, ct 2 tai v bm 1 vng trn
dng knh 8mm mi tai ri em cn ngay, trng lng khc nhau th hin mc
ph trong vim. nh gi nh hng trcn tuyn c th 48 gi sau khi bi thuc
s git chut ri ct luyn c v cm cn, tnh ra s mg tuyn c/100 g th trng
chut.
nh gi
Tnh t l % tng khi lng ca tai phi so vi tai tri v t l % c ch ph
ca l th so vi l chng theo cng thc tng t nh mc 2 .1 .1 .1.
Tnh t l % gim trng lng tuyn c ca l th so vi l chng c nh gi
tc dng lm teo tuyn c ca thuc.
20
Nguyn tc
Cc cht gy vicm kch thch gii phng cc cht trung gian nh histamin,
prostaglandin. leucotricn s lm gin cc tiu ng mch v tiu tnh mch, tng
tnh thm thnh mch. Kt qu l dch v protein huyt tng b thot ra gy ph.
Cc thuc c kh nng c ch tng tnh thm thnh mch s c tc dng gim ph,
chng vim.
2.1.3.1.G y tng tnh thm bng phenethvlainn [29]
Tin hnh
S dng chut cng c, trng lng 160-200 g, chut c chia ngu nhin
thnh cc l:
L chng: dng dung mi pha thuc
L i chiu: dng thuc chng vim bit
L Ih: dng thuc ang nghin cu tc dng chng vim
Co lng vng bng chut, tim tnh mch dung dch xanh Evan ]% vi liu 5
mg/kg. Sau 1 gi, cho chut ung thuc hoc dung mi. Sau 30 pht, gy m
chut bng clhcr ri tim trong da 0,05 ml dung dch phenethylamin 0,01% c 3 v
tr phi, tri v Ircn bng. Sau 90 pht, git chut bng ether ri tin hnh o ng
knh vng da b nhum xanh hoc ct vng da b nhum xanh em ngm vo dung
dch natri clorid 0.9% . sau khong 24 gi lc ly dch ri em o quang.
nh gi
o ng knh tnh din tch vng da b nhum mu xanh hoc tnh nng
dung dch xanh Evan thot mch. Tnh gi tr trung hnh cho tng l. Sau
tnh ti l % c ch s thot mch xanh Evan ca l th so vi l chng theo cng
thc tng t cng thc (2) mc 2.1.1.1.
21
2.1.3.2. Gy tng tnh thm thnh mch hng acid acetic [17]
Tin hnh
S dng chut nht trng, trng lng 8-22 g, chut c chia ngu nhin
thnh cc l:
L chng: dng nc mui sinh l
L i chiu: dng thuc chng vim c bit
L th: dng thuc ang nghin cu tc dng chng vim
Cho chut ung thuc hoc nc mui sinh l. Sau 30 pht, lim tnh mch
ui chut 0,2 ml dung dch xanh methylen 0.5% pha trong nc mui sinh l. Sau
3 phl. tim mng bng 4 ml dung dch acid acctic 0.3%. Sau 1 gi, gil chut, dch
bng c ht ring vo tng ng nghim, l tm, kh c v o mt quang
trn my o quang d nh lng cht mu thot ra khi lng mch [24].
nh gi
Tnh nng xanh mcthylen thot mch trn mi chut. Tnh gi tr trung
bnh cho tng l. Tnh t l % c ch thot mch ca l th so vi l chng theo
cng thc tng t cng thc (2) mc 2 . I .I .I .
2.1.3.3. Gv tng tnh thm thnh mch bng oxazolon [29]
Zentel v Topert (1994) dng oxazolon gy ihot mch xanh Evan nh gi
tc dng chng vim ti ch ca glucocorlicoid.
Tin hnh
S dng chut nht c, chut c chia ngu nhin thnh cc l:
L chng: dng dung mi pha thuc
L i chiu: dng thuc chng vicm bit
L th: dng thuc ang nghin cu lc dng chng vicm
Co lng sn tri chut ri bi vo 50 nl dung dch oxazolon 40% trong
ethanol (din tch bi khong 4 cm2) chut nhy cm vi cht kch thch. Sau
13 ngy, tim tnh mch chut 0,2 ml dung dch xanh Evan 0,5%. Ngay sau , bi
20 p.1 oxazolon 4% trong ethanol vo sn phi chut co lng (din tch bi
khong 6 cm2). Sau 3 gi, bi thuc hoc dung mi vo vng da b kch thch. Sau
22
24 gi. git chut v ct vng da b kch thch, ngm trong dung dch NaCI 0,9%
khong 24 gi, lc ly dch em i o quang bc sng 623 nm.
nh gi
Tnh nng dung dch xanh Evan thoi mch. Tnh t l % c ch s thot
mch xanh Evan ca l th so vi l chng theo cng chc tng t cng thc (2)
mc 2.1.1.1.
2.1.4. M hnh gv vim mng phi [29]
Nguyn tc
Vim mng phi l mt hin tng v vim r dch ph bin ngi. Trong
cc th nghim trn ng vl. c Ihc gy vim mng phi bng cc cht kch Ihch
nh histamin, bradykinin. prostaglandiru yu t gy mt ht t ho mast, dextran,
khng nguyn, vi khun v cc cht kch thch khng c hiu nh turpentin hay
carrageenin. Vim mng phi gy ra bi carragcenin chut c xcm l mt m
hnh gv vim cp rt tt m trong s thot dch, s di chuyn ca hch cu v
cc ch s sinh ha khc licn quan ti phn ng vim c th c o d dng trong
dch r.
Tin hnh
S dng chut cng c. trng lng 220-260 g, chia ngu nhin thnh cc l:
L chng: dng dung mi pha thuc
L i chiu: dng thuc chng vim bit
L th: dng thuc ang nghin cu tc dng chng vim.
Gy m chut bng ether. co lng bn sn phi ri lau cn, rch mt vt nh
vo trong da di chn phi trc gia xng sn 7 v 8. m rng vl rch, bc
l C lin sn ri rch m t vt nng hn trn , thng qua vt rch tim vo
khoang mng phi 0.1 ml dung dch carragecnin 2%, vic tim phi c thc hin
nhanh trnh gy tn Ihng phi, vt thng c ng kn li bng mt kp.
Sau cho chut dng thuc hoc dung mi vo cc thi im 1, 24, 48 gi
sau khi lim carragccnin.
72 gi sau khi tim carragcenin tin hnh git chut bng cthcr, ht hc dch r
mng phi vo trong mt ng c chia vch xc nh th tch dch r.
23
Ngoi m hnh trn, c th gy vicm mng phi chut cng bng tinh du
thng vi cch tin hnh v nh gi kt qu tng t [ 19|.
nh gi
Tnh gi Ir trung bnh ca th tch dch r vim mi l v so snh l th vi
l chng. Dng cc liu khc nhau c ih xc nh c ED50.
Mt s thng s c th xc nh:
Xc nh s lng hch cutrong dch r bng mt my dm
Xc nh hot lnh ca cc enzym trong lysosom
Xc nh bronectin
X c nh PGE2
Nguyn tc
M hnh gy ban bng tia u v c Wilhelmi m t ln u tin (1949),
ng nhn thy kh nng lm chm s pht trin ban do tia u v ca
phenylbutazon v cc thuc chng vim khng steroid. Sau cc nh khoa hc
khc m rng v ci tin phiig php ny bng cc cch kch thch khc.
Tin hnh
S dng chut lang trng c 2 ging, trng lng khong 350 g, chut c
chia ngu nhin thnh cc l:
L chng: dng dung mi pha thuc
L i chiu: dng thuc chng vim bit (indomethacin liu 1,5
mg/kg: phenylbutazon liu 4 mg/kg: acid acetylsalicylal liu 60 mg/kg).
L th: dng ihuc ang nghin cu tc dng chng vim.
Trc khi tin hnh th nghim 18 gi, chut dc co lng 2 bn sn v Irn
lng. Cho chut ung 1/2 lng thuc nghin cu hoc dung mi. Sau chut
c t vo trong ] li da c c 16 (kch thc 1.5 X 2.5 cm) cho php tia
u v ch chiu vo vng ny. S dng n t ngoi nguyn bn Hanau 600W, lm
nng n 30 pht trc khi dng v t n c nh, cch cc con vt 20cm. Chiu
tia u v trong 2 pht ri cho chut ung nt 1/2 lng thuc hoc dung mi cn li.
Ban c ghi li ti thi im 2 gi v 4 gi sau khi chiu tia u v .
24
nh gi
Da vo phng php tnh im nh gi mc ban trn mi chut :
0 = khng ban
1 = ban yu
2 = ban mnh
4 = ban rt mnh.
Tnh im trung bnh ca mi l. Sau tnh t l % c ch ban ca l th
so vi l chng theo cng thc tng t cng thc (2) mc 2 .1 .1 .1.
Nhng chut vi kt qu l 0 v 1 c xem l c bo v. Cc kl qu
thu c sau 2 v 4 gi c th s b cho bit khong thi gian tc dng v c th
tnh c EDS().
2.1.6. M hnh to ti II ht [29, 39]
Nguyn tc
M hnh to ti 11 ht do Selye pht minh (1953) v c Roberl v Nezamis
ci tin (1957). M hnh s dng du ba u [ cht kch thch gy ra mt vim bn
cp tng t tnh trng vim v khun do tng mt th tch ln dch Ihol mch.
Tin hnh
S dng chut cng c 2 ging, trng lng 150-200 g, chut c chia ngu
nhin thnh cc l:
L chng: dng dung mi pha thuc
L i chiu: dng thuc chng vim bit (indomethiicin)
L th: dng Ihuc ang nghin cu tc dng chng vim
Lng chut dc co lng v st trng. Gy m chut, dng mt kim rt mng
tim 20 ml khng kh vo vng da gia lng. Sau , tim 0.5 ml dung dch du ba
u 1% trong du vrng vo trong ti khng kh. trnh lt kh. Sau 48 gi. rt
khng kh trong ti. Sau , hng ngy cho chut dng thuc hoc dung mi.
nh gi tc dng ti ch, thuc c tim trc tip vo ti khng kh cng thi
25
nh gi
Tnh th tch trung hnh dch thu c ca cc l. Tnh ti ] % c ch vim ca
l th so vi l chng theo cng thc tng t cng thc (2) mc 2.1.1.1.
2.2. M HNH C.Y V IM MN TNH
2.2.1. M hnh gy u ht (hc nghim
Nguyn tc
Khi a vo c thc mt vt l khng c kh nng hp thu c nh amian.
bng...th c the s phn ng bng cch tp trung nhiu loi t ho lo ra m bo
li v nguyn bo si bao quanh vt l, to Ihnh mt khi u gi l u ht thc
nghim. Qu trnh tin trin to u ht thc nghim tng t vi tin trin ca mt
vim mn tnh. Mt thuc c kh nng c ch s hnh thnh u ht s gp phn iu
tr cc bnh vicm mn lnh. Vi cc cht kch thch khc nhau ta c cc m hnh gy
u ht thc nghim khc nhau.
2.2.1.1. (y u ht thc nghim bng amian [1 8 ,1 1 ]
M hnh tin hnh theo phng php ca Ducrol. Julou v cng s (1963).
Tin hnh
S dng chut cng trng c 2 ging, trng lng 100-140 g. chut c chia
ngu nhin thnh cc l
L chng: dng nc mui sinh l
L i chng: dng Ihuc chng vim bit
L th: dng thuc ang nghin cu lc dng chng vim.
Dng I mu si amian ng knh khong 2 mm. trng lng 30 I mg c
v trn v sy tit khun trong 2 gi 160"C.
Chut c gy m, co sch lng vng lng pha trn. Dng mi ko bm
mi l nh da ri un mi ko vo tch da lng ra khi c. cy si amian vo
26
ni bc lch. t kp hoc khu ni lin ch m trn lng. Phu thut lin hnh
trong iu kin v khun.
Cho chut ung hoc tim di da thuc hoc nc mui sinh l vo mi bui
sng trong 5 ngy lin lc, ln du cho thuc ngay sau khi cy si amian. Chiu
ngy th 5 k t ngy cy amian. git chut hng cloroform. bc tch khi u v cn
ti ngay.
nh gi
Tnh trng lng thc ca u ht bng Irng lng cn c tr i trng lng
ca si amian cy vo. Tnh trng lng trung bnh ca u ht cc l. Tnh t l %
c ch u ht ca l th so vi l chng.
2.2.1.2. (jrv u ht hc nghim bng bng [29]
y l m hnh gy u ht thc nghim u tin do Mcicr v cng s (1950)
tin hnh.
Tin hnh
S dng chut cng c, trng lng Irung bnh khong 200g, chia ngu nhin
thnh cc l
L chng: dng nc mui sinh l
L i chiu: dng thuc chng vicm bit
L th: dng thuc ang nghin cu tc dng chng vicm
Gy m chut, co lng lng v st trng bng ethanol 70". Rch 1 vt tht
lng, dng mt km to nhng ng di da v t lit vin gc bng c tit
Irng vo c 2 bn xng b vai. Cho chul ung thuc hoc dung mi lin tc
trong 7 ngy. Ngy th 8, git chut, bc tch u ht v sy kh n khi lng
khng i ri cn.
Theo kinh nghim ca cc nh nghicn cu th s to thnh u ht s mnh hn
khi gc bng c tm carrageenin.
nh gi
Tnh trng lng kh thc ca u ht ri tnh gi tr trung hnh ca mi l. Tnh
t l % c ch u ht ca l th so vi l chng.
2.2.1.3. Mt s m hnh gy 11 ht thc nghim khc [29, 39]
27
M.phlei) cht c pha trong paran lng hoc du khong hoc du thc vi.
Khi tim cht ny vo trong c th chut cng s gy hi chng ging vim khp.
Tin hnh
S dng chut cng c trng, trng lng trung hnh khong 200 g, chut
c chia ngu nhicn Ihnh cc l:
L chng: dng nc mui sinh l
L i chiu: dng thuc chng vim bit
L th: dng thuc ang nghin cu tc dng chng vim.
Cho chut ung thuc hoc nc mui sinh l. Sau 1 ngy, o dy bn chn
phi sau ca chut. Tim vo gan bn chn phi sau 0.05 mi cht b tr. Cho chut
ung thuc 13 ngy lin tc k t khi tim cht b tr. n ngy th 13, o dy
bn chn phi sau ca chut.
VVard v cng s (1962) tin hnh gy vim a khp bng cht sp D phn
lp t trc khun lao vi cch lm tng l trcn.
nh gi
Tnh li l % tng dy chn chul trc khi tim v 13 ngy sau khi licm
cht b tr. Sau tnh trung bnh t l % tng dy chn ca cc chut trong mi
l. T tnh t l % c ch tng dy ca l th so vi l chng. Cc cng thc
tnh tng t mc 2.1.1.1.
28
Tin hnh
S dng chut cng trng, trng lng 120-150 g, chut c chia ngu nhin
thnh cc l
L chng: dng dung mi pha thuc
L i chiu: dng thuc chng vim bit
L th: dng thuc ang nghin cu tc dng chng vim.
Chun b Mycopasm arthritis: nghin mt mnh sarcom lympho Murphy c
cha Mycopiasma arthris. Sau pha thnh hn dch trong NaCl 0,9% v cho
thm 400.000 n v penicillin v 1.000.000 n v colislin mclhansulonat. Hn
dch c ly tm trong 30 pht, gi li dch ni pha trn.
To dch r gy vim khp: Tim 30 ml khng kh v khun vo di da lng
chut e to 1 ti kh, ri tim 2 ml dch cha Mxcopsma arthritis thu c trn
vo ti kh. Sau 6-10 ngy, ht dch t trong ti, dch ny c cha nhiu vi khun
nh gi
Quan st hng ngy cc nhm khp: khp chy-e chn trc v sau; khp
xng c chn trc v sau; khp gia cc t ngn chn trc v sau. T xc
nh ch s vim khp da vo phng php tnh im:
0: bnh thng
1: ban nh
29
2: va ban d va sng
3: sng ty.
Cng s im ca cc ngy ta c mt ch s vim khp.
Tnh t l % c ch vim khp ca l th so vi l chng theo cng Ihc tng
t cng thc (2) mc 2.1.1.1.
2.3. M HNH NGHIN CXi c C H CHNG VIM
2.3.1. Gy kt tp bch cu a nhn [29]
Nguyn tc
Khi c lc nhn gy vim tn cng vo c th. chng s to ra cc cht ha
ng ng thu ht v tp trung bch cu li ni c cc cht ha ng ng . S c
mt qu nhiu bch cu s lm khuch i phn ng vim gy ra nhng tn thng
trm trng cho m v c th. V vv. mt trong nhng c ch chng vicm l c ch
ha ng ng bch cu. Trong m hnh ih nghim ny s dng cht gy ha ng
ng bch cu l fo)Tnyl-L-mcthionyl L"lcucyl-L-phcnylamin (FMLP).
Tin hnh
Chun b t bo bch cu a nhn: Tim vo mng bng chut cng 10 ml
dung dch casein natri 6%. Sau 17 gi. Ihu dch r mng bng to hn dch cc
t bo bch cu a nhn. Cc t bo c ra 2 ln trong dung dch nc mui ng
trng ri pha thnh hn dch vi nng 15 X 106 t bo/ml.
Gy kt tp bch cu a nhn: Thuc th v thuc i chiu (pcntoxiphvllin)
c ha tan trong dung dch nc mui ng trng. Hn dch t ho c li vi
thuc trong 10 pht ri thm FMLP pha trong dimethvl sulfoxid (DMSO) gv kt
p bch cu. S kl tp bch cu a nhn c thc hin irong my tp trung Born.
nh gi
So snh s kt tp bch cu da nhn gia nhm th v nhm chng da Irn
kt qu o t my.
2.3.2. Gy ha ng ng i thc bo [30]
Nguyn tc
M hnh s dng mt cht gv ha ng ng i thc ho v qua nh gi
kh nng c ch ha ng ng i thc bo ca thuc.
30
Tin hnh
S dng chut cng c. trng lng 200-220 g. Dng Ihioglycolk l cht
gy ha ng ng i thc bo.
Chun b cc t bo i thc ho: tim mng bng chut 5 ml canh
thi og lyco Hat 3%. 3 ngy lin tip sau khi tim thioglycollat cho chut ung thuc
hoc nc mui, Vo ngy Ihr 4, ihu ly cc t bo trong dch r mng bng bng
cch ra khoang mng bng vi dung dch nc mui ng trng. Cc t bo c
ra 2 In vi nc mui ri pha thnh hn dch nng 1X 10fi t bo/ml trong mi
trng lnh RPM I-1640 khng c phcnol v c b sung huyt thanh b 10%.
pcnicillin 100 Ul/ml v streptomcin 100 ig/ml.
Gy ha ng ng i thc bo: cc t ho c 3 7 c v 5% C 0 2 trong 2
gi cho cc i ihc bo bm vo b mt a nui cy. Cc t bo khng bm sc
b loi b hng cch ra mnh vi nc mui dng trng m. 90% cc t bo bm
vo a l cc i thc ho.
nh gi
S lng i thc bo c m bng my huyt tc k. So snh kt qu gia
mu th v mu chng.
2.3.3. Th nghim v cc cht chuyn ha ca acid arachidonic [29]
2.3.3.I. Th nghim oxv ha acid arachidonic bi CO X-1
Tin hnh
Ly 50 Jil cnzym COX-1 ti t hp tinh khit nng 1 ng/ml pha vo trong
Tris-HCl 100 mM, EDTA 0,5 mM pH 8,0. phcnol 1 mM, hcmatin 1-iM ri vi 2
dung dch cht c ch hoc DMSO (mu chng) trong 15 pht. Sau phn ng
c bt u bng cch thm 5 |j1 [ MC1- acid irachidonic 1 f.iM (0.005 jiQ) thu
c nng cui cng l 0.1 jM. nhit phng. Sau 7 pht, phn ng c
dng li hng cch thm 5 [li MCI ] M v 50 jLil acetonitril. Ly 50 nl mu phn ng
cho ln ct sc k HPLC tch cc cht. Cc cht chuyn ha ca acid Ltraehidonie
v acid arachidonic c tch ra v c nh lng bng mv pht hin sc ph
phng x.
31
nh gi
Tnh t l % acid arachidonic chuyn ha thnh prostaglandin. So snh ti l
gia mu th c cht c ch v mu chng khng c cht c ch.
2.3.3.2. To cc eicosanoid t l4C-acid arachidonic t bo iu cu
Eicosanoid l tn gi chung cho cc sn phm chuyn ha ca acid
arachidonic, bao gm prostaglandin. leucotrien, thromboxan. Prostaglandin gy tng
tnh thm thnh mch, gy ph. han . gy au. Lcucotrien c tnh ha ng ng
bch cu. kch thch hm dnh t ho bch cu vo l bo ni m...Thromboxan
kch thch s kt tp tiu cu. Do , c ch s hnh thnh cc cht ny l mt c
ch chng vim quan trng.
Tin hnh
Chun b cc t bo tiu cu: ly mu tnh mch cnh tay ca ngi tnh
nguyn khe mnh v tp trung trong cc ng nghim cht do c sn nalri citrat
(nng cui cng l 0,38% ). Khng qu 1 gi trc khi lm th nghim, ly tm
mu 100 g trong 15 pht thu c huyt tng giu tiu cu (khong 2,5 X 10"
tiu Cu/I),
bo q u n
20c.
10 4 Ci/1). Sau 5 phl. dng phn ng hng cch thm 0.5 ml aceton lm lnh/o.l
ml HC1 IN, lm lnh ti 0"C v chit 2 ln vi 3 ml ethylacetat/ln. Dch chit c
lm bav hi dung mi. sau ha tan cn trong 0,2 ml mcthanol ri a ln ct sc
k HPLC tch cc cht. Xc nh cc l4C-eicosanoid to thnh bng my plt
hin nhp nhy.
nh gi
So snh s to thnh T X B : v PGE gia mu th v mu chng.
32
Nguyn tc
M hnh s dng lipopolysaccharide (LPS) kch thch sinh PGE2. Cch tin
hnh do Herrmann v cng s xut ln u (1990). sau Weithmann v cng s
ci tin (1994).
Tin hnh
Nui cy cc t bo hch cu a nhn trung tnh vi ml 2.5 X 109 t bo/1
trong mi trng RPMI 1640 c b sung natri pyruvat 1 mmol/l. huyt Ihanh b 5%,
glutamin 2 mmol/1 v 100 Ul/ml pcnicillin/slreptomycin. Tin hnh bch cu a
nhn trung tnh trong mi trng RPMI 1640 vi acid acctyl salicylic 100 |amol/l
trong 60 pht (37c, 5% C 0 2). v sau ra 4 ln vi mi trng. Lv 0,25 ml mu
(2,5 X 10 bch cu a nhn/1 mi trng) vi LPS 0,1 mg/ml cng vi thuc Ih
trong 18 gi (ca 96-well, 37c. 5% c o ? )- To cc eicosanoid bng cch thcm 7 X
10'5 mol/1 cht mang ion calci A 23 187. 30 pht 37"C. Sau cc a c ly
tm 400 g trong 15 pht. PCiE, to thnh nm trong phn ch ni pha trn, c
xc nh bng ki ELISA.
nh gi
So snh nng PGE2 to thnh gia mu c thuc ih v mu chng khng
c thuc.
2.3.3.4. To leucotrien B4 t bo bch cu
Tin hnh
Chun b cc t ho hch cu: ly 40 ml mu ti citral ha c trn ln
vi 8 ml m PM16 gm c dcxtran 6% (trng lng phn t l 480 000) v c
f nhit phng trong 1 gi. Dch ni pha trn gm c cc t ho hch cu, ly
dch ra v pha long 1:1 vi PM16 ri ly tm 300 g trong 15 pht. Phn cn c
ha trong P M 16 v iu chnh c 10' t bo/1.
To leucotrien: ly 0,3 ml hn dch t bo trn tin hnh th nghim
chuyn ha acid arachidonic ni sinh thnh LTB4 ( 37"C). ng nghim phn ng
gm c 2 mrnol/1 CaCI2, 0,5 mmol/l MgCU v thuc nghin cu. Sau khi 15 pht,
phn ng c ht u bng cch thcm 12,5 g cht mang ion calci 23 187 v 2 g
33
glutathionc. Sau 5 phl, phn ng c dng li bng cch thm 30 il HCI 0.1 M
0l,c . Sau ly lm 2 pht C. phn dch ni pha trn c cm i sc k HPLC
tch lcucotrien B4. Dng cc thuc chun bit xc nh cc ng phn cis-,
trans-, v Cpi-LTB4. Vic phn hit 3 ng phn c th theo di hng phcp o quang
hc sng 278 nm.
nh gi
So snh kt qu gia mu c thuc th vi mu chng khng c thuc v mu
c thuc bil Cc dng.
2.3.4. Gy gii phng cc cyokin t t bo bch cu [29]
Nguyn tc
Cc cvtokin i din cho mt nhm cc peptid c hot tnh sinh hc cao.
Chng lin quan ti nhicu qu trnh t bo nh phn ng vicm. min dch v nhiu
p ng khc. Vic kha cc 1L-1 v TNF-tt gip iu tr thnh cng bc u
trn cc bnh nhn vim khp dng thp, vim rut hoc cc bnh thi manh ghp.
M hnh gy gii phng cytokin c dng pht hin cc thuc m tc dng vi
lipopolysaccharid trong qu trnh gii phng cytokin t t bo bch cu om nhn,
Tin hnh
Chun b t ho hch cu: ly 10 ml mu ti cilrat ha pha long 1:1 vi
m PM 16 v c lt vi 15 ml dung dch Lymphoprcp*. sau ly tm 400 g
trong 30 pht 20 "C. Phn t bo l mt vng trng xut hin gia 2 pha v c
ly ra cn thn bng 1 ng tim, pha long 1:1 vi PM 16 ri ly tm li trong 15
pht. Cn c ra sch vi 10 mi trng RPMI 1640 c thm L-glutamin 300
mg/1. Phn t bo ra c cho vo trong 1 ml mi trng RPMI 1640 c Ihm
L-glutamin
300
mg/1.
HEPES
25
mmol/l.
huyt
thanh
5%
34
nh gi
Xc nh nng cytokin v so snh gia mu dng thuc vi mu chng khng
dng thuc.
35
3. BN LUN
3 .1 .Bn lun v m hnh nghicn cu tc dng chng vim ca thuc
36
IT 1
hnh khc;
37
3.1.1.4.
M hnh gy ban
3.1.1.5.
M hnh to ti u ht
39
l giai on thm dch, xut hin irong 3 gi u tin, vin bng s ngm dch v
t bo ha; giai on 2 l giai on r dch, xut hin sau 3-72 gi cy bng, pha 3
l pha tng sinh vi s xut hin ca collagen trong u ht. Do c th nghin cu
c ch lc dng ca cc Ihuc thng qua cc giai on ny. M hnh ny rt nhy
vi cc thuc chng vim slcroid.
40
41
M hnh gy vim cp v bn cp
Theo chng ti, mun chng minh mt thuc (thuc y hc c truyn hay hot
cht mi) c tc dng iu tr vim, Ire ticn nn tin hnh chng minh tc dng
chng vim trn cc m hnh gy vim cp v bn cp. Cc kt qu thu c trn
cc m hnh ny s cho php nh gi mt cch s b thuc c lc dng chng vicm
hay khng v mc tc dng ca chng. Ch tiu nh gi cc ih nghim ny
ch yu thng qua kh nng c ch ph (chn chut hoc tai chut) hoc thng
42
qua lm gim cc du hiu ban hoc thng qua c ch s thot mch ca huyt
tng hoc thng qua c ch s tng lit dch r vim...
43
44
4. K T LUN V XUT
4.1. Kt lun
ca thuc ang c p dng ti Vit Nam v trn Th gii, chia thnh 3 nhm:
+ M hnh gy vim cp v hn cp gm:
M hnh gy ph bn chn chut
M hnh gy ph tai chut
M hnh gy tng tnh thm thnh mch
M hnh gy vicm mng phi
M hnh gy ban
M hnh to li u hl
+ M hnh gy vim mn tnh gm:
M hnh gy u ht thc nghim
M hnh gy vim a khp thc nghim
+ M Knh nghin cu c ch chng vim gm:
Gy kt tp bch cu a nhn
Gy ha ng ng i thc bo
Th nghim v cc cht chuyn ha ca acid arachidonic
Gy gii phng cytokin t t bo bch cu.
ti nh gi tng m hnh, kh nng p (lng m hnh trong nghin
cu tc dng chng vicm ca thuc.
ti xut hng la chn cc m hnh nghin cu p dng vo
iu kin thc t ca Vit nam
4.2. xut
T kt qu thu c v da vo icu kin c Ihc, chng li nhn thy hon
thin h thng cc m hnh nghin cu tc dng chng vim phc v cho nghin
cu th cn tip tc:
Nghin cu su hn v c ch phn t ca cc m hnh t a ra
c c ch tc dng ca Ihuc.
45
46
T I L I T H A M K H O
Ti liu ting Vit
1.
V Hng Anh (1999), Gp phn nghin cu tc dng chng vim ca ch' phm
cha papain. Lun vn Thc S Dc hc
2.
4.
5.
6.
7.
8.
9.
Borel J. B., F-X Maquart. Ph. Gillcry. M.Exposito (2006), Ha sinh cho thv
ngn
{Lonicera japonica
Thunb..
Caprioliaceae)
kt
hp
vi
a-
26. Ana Maria Diaz ct al. (2000), i n vitro anti-inflammatory activity of iridoids and
triterpenoid compounds isolated from Phiiiyrea latifolia L.\ iol. Pharm. BulL
Vol.23. No. 11, pp. 1307-1313.
27. Antonio Navarro, Bcatriz Dc Las Hcras and Angcl Villar (2001), AntiinAammatory and immunomoulating ppropcrlics of a stcrol action from
Sideritis foetens Clem., Biol. Pharm. Bu . Vol. 24, No. 5, pp. 470-473.
28. Dy M.. Debray-Sachs M.. Kamoun p., Hamburgcr J. (1978), Effcct of
thioglycollate on macrophage lysosomal enzymes.. Biomedinc . 29(5), pp. 167170.
29. Gcrhard H. Vogcl (Ed.) (2002). Dru discovery and cvluaiion- pharm acoloca
34. Jing Ming J1A. Chun Fu w u , * Wen LU. Hai Y U Yue HAO. Jian Hua ZHENG,
and Yu Rong JI (2 0 0 5 ), AiUiinf]ammatory and analgesic actvitics ol' thc tissuc
cuiture of Saussitrca invoucrata, Bioi. Pharm. BnlL 28(9). pp. 1612 1614
35. John M.Young. Doreen A Spires. Charles J. Bedord. Bonnie Wagncr. Stcphcn
J. Ballaron and Lawrcncc M. de Young (1984), The mouse car inflammatory
response to topical arachidonic acid, .oitrn o f nvestqative Dennatology&2, pp.
367-371
36. Juhlin.L , Shroot. B (1992). Effect of drugs on the early and hite phase v
erythema, Acta-Derm-VenereoJ2Q ). pp. 222-3
37. Maria Alejanra HOSSEN et al.(2006), CalTeic acid inhibits compound 48/80-
development
of
an
expcrimcntal
tramatic
paw edema
in thc
rai".
PH LC
1.
M i tr n g R P M I 1640
Ca(NO,)2
L-Isoleucine
Polic acid
M g S 0 4 (anhyd)
L-Leucine
Glutathionc
KCI
L-Lvsinc HC1
mvo-Inositol
NaHCO,
L-Methionine
Niacinamide
NaCI
L-Phenylalanine
D-Pantothenic acid
Na2H P 0 4 (anhyd)
L-Proline
Pvridoxinc
L-Argininc
L-Serine
Ribolavin
L-Asparagine
L-Thrconine
Thiaminc HCI
L-Aspartic acid
L-Tryptophan
Vitamin B12
Cystinc 2HCI
L-Tyrosine 2Na
D-Glucosc
L-Glulamic acid
dihydrate
HEPES
L-Glutaminc
L-Valine
Phcnol rcd
Glycine
p-Aminobcnzoic acid
L-Glulaminc
L-Histidine
D-Biolin
NalCO,
Hydroxy-L-proline
2.
L y m p h o p rep "
Sodium Diatrizoate
9,1% (w/v)
Polysaccharide
5.7% (vv/v)