Abstract: OBJECTIVE: To investigate the involvement of growth arrest specific 5(GAS5), a long non-coding RNA, in the anti-hepatic fibrosis process induced by Dahuang Zhechong pill(DHZCP) in rats.METHODS: Thirty adult rats were divided into three groups, including a control group, a CCl4-induced fibrosis group and a DHZCP-treated fibrosis group. Hematoxylin-eosin and Masson staining were used for histopathological study. Serum enzymes, cytokines and cell proliferation were assayed using commercially available kits. A GAS5 lenti-virus vector was constructed to further investigate the role of GAS5 in the anti-hepatic fibrosis effect of DHZCP in rats.RESULTS: Our results revealed that the proliferation of hepatic stellate cells cultured in serum derived from rats treated with DHZCP was significantly decreased, compared with cells treated with serum from the untreated rats. DHZCP alleviated the CCl4-induced hepatic fibrosis. Additionally, DHZCP can restore the expression of GAS5,which was significantly decreased in the CCl4-induced group, and markedly suppress the expression of p-p38 and p-Erk induced by CCl4, but not p-Jnk. Cell proliferation was significantly arrested when cells overexpressed GAS5. Thus,DHZCP can inhibit the expression of p-p38 and p-Erk, while GAS5 can only inhibit the expression of p-Erk.CONCLUSIONS: DHZCP can alleviate hepatic fibrosis by increasing the expression of GAS5 to suppress p-Erk and regulating other factors to inhibit p-p38.

Key words: RNA,long noncoding, Liver cirrhosis, Mitogen-activated protein kinase kinases, Dahuang Zhechong pill