[Prophylactic and therapeutic effect of oxymatrine on D-galactosamine-induced rat liver fibrosis].
OBJECTIVE
To investigate the prophylactic and therapeutic effect of oxymatrine on experimental liver fibrosis and to reveal its mechanism.


METHODS
By establishing D-galactosamine-induced rat liver fibrosis model, we observed the effect of oxymatrine on serum and tissue biochemical indexes, content of liver hydroxyline, expression of TGF?1 mRNA and changes of tissue pathology.


RESULTS
There was a decline of liver hydroxyline and serum AST and ALT in oxymatrine group compared to those of the D-GalN group. The hydroxyline content in oxymatrine pretreatment group was (0.50 0.11)mug/mg compared with (0.99 0.14)mug/mg in D-GalN group (t=8.366, P<0.01). The content in oxymatrine treatment group was (0.44 0.04)mug/mg compared with 0.70 0.06 in D-GalN group (t=9.839, P<0.01). The SOD activity was (149.81 15.28) NU/mg in oxymatrine pretreatment group and (95.22 16.33) NU/mg in the model group (t=7.309, P<0.01); (157.68 19.54) NU/mg in the treatment group compared with (119.88 14.94) NU/mg in the model group (t=4.348, P<0.01). MDA in the pretreatment group was (2.06 0.17) nmol/mg, lower than (4.57 0.37) nmol/mg in the model group (t=17.529, P<0.01). In the treatment group, it was (1.76 0.24)nmol/mg, lower than (3.10 0.17) nmol/mg in the model group (t=12.697, P<0.01). TGF?1 mRNA reduced in the pretreatment and treatment groups as compared with that in the model group (0.21 0.01 vs 0.50 0.01, t=48.665, P<0.01; 0.18 0.02 vs 0.38 0.01, t=22.464, P<0.01). Electron microscopy showed that oxymatrine group had milder hepatocyte degeneration and less fibrosis accumulation than did the model group. Microscopy revealed wide septa expansion from the portal area to the central venous, piecemeal and confluent necrosis and pseudo-nodular formation in part of the lobular in the model group. While in oxymatrine group these lesions were much improved.


CONCLUSIONS
Oxymatrine shows prophylactic and therapeutic effect in D-galactosamine induced rat liver fibrosis. This is partly by protecting hepatocyte and suppressing fibrosis accumulation through anti-lipoperoxidation.
Shanghai Digestive Disease Institute, Renji Hospital, Shanghai 200001, China.
Wenzhuo
W
Yang
Minde
M
Zeng
Zhuping
Z
Fan
Yimin
Y
Mao
Yulin
Y
Song
Yitao
Y
Jia
Lungen
L
Lu
Cheng Wei
CW
Chen
Yan Shen
YS
Peng
Hong Yin
HY
Zhu
D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D002126:Calcium Hydroxide / Q000378:metabolism; D018890:Chemoprevention; D004195:Disease Models, Animal; D005688:Galactosamine; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008111:Liver Function Tests; D008297:Male; D011807:Quinolizines; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D000093842:Matrines
D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D002126:Calcium Hydroxide; D005688:Galactosamine; D011807:Quinolizines; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D016212:Transforming Growth Factor beta; C018571:Hydroxyline; C037573:oxymatrine; D000093842:Matrines