Effect of artesunate on rat liver fibrogenesis in vitro and in vivo / 中国药理学通报

ABSTRACT

Aim To study the effect of artesunate on immuno-injured hepatic fibrosis induced by bovine ser-um albumin in rat model and the effect of artesunate on hepatic stellate cells ( HSCs ) proliferation, so as to provide experimental evidence for clinical application of artesunate and the treatment of hepatic fibrosis. Methods The model of immuno-injured hepatic fibro-sis induced by bovine serum albumin was established in Wistar rats. Rats were randomly divided into 5 groupsnormal group, model group, low dose of arte-sunate, middle dose of artesunate and high dose of ar-tesunate. Drugs were given to the corresponding thera-peutic groups, and then were continued once a day for two months. Distilled water was given to the rats of normal and model groups according to the same meth-od. Liver tissues were used for measuring the content of collagen, the rat serum activities of albumin( Alb) , alanine aminotransferase ( ALT ) and aspartate amin-otransferase(AST). Liver tissue’ s pathological chan-ges were observed by HE and collagen staining. Isola-ted and cultured rat primary HSCs in the flask for 10 days to make cells activated, MTT assay was used to detect rate of cellular proliferation; concentration of hydroxyproline in supernatant was detected by digestive method; the expression of p53 was investigated by Western blot and RT-PCR. Results Serum levels of Alb in model group were significantly lower ( P <0. 05 ) , and levels of ALT and AST in model group were significantly higher ( P <0. 05 ) compared with normal group. Levels of AST in low, middle and high dose groups(3. 2, 9. 6, 28. 8 mg·kg-1 ) were signifi-cantly lower(P <0. 05) compared with model group, and levels of ALT in high dose groups were significant-ly lower(P<0. 01) compared with model group. The contents of collagen in model groups were significantly higher(P<0. 01) compared with normal group, while the contents of collagen in therapy groups significantly decreased ( P < 0. 05 ) compared with model group. Activated HSCs treated with various concentrations of artesunate (150, 175, 200 μmol·L-1 ) were inhibi-ted on dose and time-effect relationships. Production/secretion of hydroxyproline decreased after HSCs was treated by artesunate for 24 h; the expression of p53 was up-regulated showed by Western blot and RT-PCR in artesunate treated cells. Conclusion Artesunate brings about anti-fibrosis in vitro and in vivo by increas-ing the expression of p53 .