Abstract:

Objective To investigate the therapeutic effect of rhein lysinate (RHL) on the liver fibrosis in the cholestatic model rats, and to expound the molecular mechanisms of RHL in treatment of liver fibrosis in the cholestatic rats. Methods 35 rats were divided into control group, model group, 35 and 70 mg·kg^-1 RHL treatment groups, and lysine group(n=7).The rat models of cholestatic hepatic fibrosis were established by bile duct ligation (BDL) method.The activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the levels of total bile acid (TBA), total bilirubin (TBIL) were detected by using an automatic biochemical analyzer;the pathological changes of liver tissue of the rats in various groups were observed by HE staining;the content of fiber in liver tissue was observed by Masson's trichrome stain;the level of hydroxyproline (Hyp) was detected by microplate reader according to the instruction of respective kits;the expression of α-smooth muscleactin (α-SMA) was detected by immunohistochemical staining;the expression level of α-SMA was detected by Western blotting method. Results Compared with control group, the ratio of liver weight to body weight and the activities of AST and ALT, the levels of TBA and TBIL in serum of the rats in model group were increased (P<0.05);the hepatic lobule structure of hepatic tissue was destroyed, and the fibrous tissue hyperplasia was found, the Hyp level was also increased(P<0.05);the immunohistochemical staining Results showed that α-SMA expressed in cell membrane and cytoplasm, and the Western blotting Results showed that the expression level of α-SMA protein was increased(P<0.05). Compared with model group, the ratio of liver weight to body weight and the activities of AST, ALT and the levels of TBA, TBIL in serum in 35 and 70 mg·kg^-1 RHL groups were significantly decreased(P<0.05);the liver histopathological examination found that the fibers of the rats in 35 and 70 mg·kg^-1 RHL groups were reduced, and the levels of Hyp were also decreased(P<0.05); the immunohistochemistry and Western blotting Results showed that the levels of α-SMA protein were reduced(P<0.05). Conclusion The hepatic protection of RHL is correlated with the inhibition of the activation of hepatic stellate cells, fibrosis and fiber accumulation of liver tissue.It is concluded that RHL would be a therapeutic drug for the patients with cholestatic liver fibrosis.

Key words: cholestasis, liver fibrosis, rhein lysinate