Effects of oxymatrine on experimental hepatic fibrosis and its mechanism in vivo.
OBJECTIVE
Hepatic fibrogenesis has close relation with hepatic stellate cells (HSC) and tissue inhibitors of metalloproteinase (TIMP). Oxymatrine (OM) is a kind of Chinese herb that is found to have some effects on liver fibrosis. We aimed to determine the effects of OM on hepatic fibrosis and explore the possible mechanism.


METHODS
Thirty-two rats were randomly divided into four groups; 16 were used to develop hepatic fibrosis by carbon tetrachloride (CCl4) and treated with or without OM, and 16 were used as controls. The expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and alpha-smooth muscle actin (alpha-SMA) in the livers of rats was detected by immunohistochemical assay. Liver pathology was determined by H and E staining and reticulum staining.


RESULTS
In CCl4-injured rats, the normal structure of lobules was destroyed, and pseudolobules were formed. Hyperplasia of fibers was observed surrounding the lobules. While the degree of fibrogenesis in liver tissues was significantly decreased in those rats with OM-treatment compared with those without OM treatment. The pseudolobules were surrounded by strong, multi-layer reticular fibers, which netted into pseudolobules in CCl4-injured rats, however, there was a significant decrease in reticular fibers in OM-treated rats. The expression of TIMP-1 in hepatic cells was weak in control groups, but strong in CCl4-injured groups, however, the expression of TIMP-1 was significantly inhibited by OM (F = 52.93, P<0.05). There was no significant change in the expression of alpha-SMA between CCl4-injured rats with or without OM treatment (F = 8.99, P>0.05).


CONCLUSIONS
OM effectively inhibits CCl4-induced fibrogenesis in rat liver tissues, probably by reducing the expression level of TIMP-1.
Shi
Guang-Feng
GF
Department of Infectious Diseases, Hua Shan Hospital, Fu Dan University, Shanghai 200040, China. gfshi@shmu.edu.cn
Li
Qian
Q
D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D002252:Carbon Tetrachloride Poisoning; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D011807:Quinolizines; D051381:Rats; D017207:Rats, Sprague-Dawley; D000093842:Matrines
D000470:Alkaloids; D003094:Collagen; D004365:Drugs, Chinese Herbal; D011807:Quinolizines; C037573:oxymatrine; D000093842:Matrines