Emodin protects rat liver from CCl4-induced fibrogenesis via inhibition of hepatic stellate cells activation

被引:0
作者
Miao-Xian Dong
机构
基金
中国国家自然科学基金; 美国国家科学基金会;
关键词
Emodin; Hepatic fibrosis; Transforming growth factor-β1; Smad4; Hepatic stellate cell; α-smooth muscle actin;
D O I
暂无
中图分类号
R575.2 [肝硬变];
学科分类号
1002 ; 100201 ;
摘要
AIM:To investigate the role of emodin in protecting the liver against fibrogenesis caused by carbon tetrachloride (CCl4) in rats and to further explore the underlying mechanisms.METHODS: Rat models of experimental hepatic fibrosis were established by injection with CCl4; the treated rats received emodin via oral administration at a dosage of 20 mg/kg twice a week at the same time. Rats injected with olive oil served as a normal group. Histopathological changes were observed by hematoxylin and eosin staining. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and hepatic hydroxyproline content were assayed by biochemical analyses. The mRNA and protein relevant to hepatic stellate cell (HSC) activation in the liver were assessed using real-time reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, western blotting and enzyme-linked immunosorbent assay.RESULTS: The degree of hepatic fibrosis increased markedly in the CCl4 group compared to the normal group (P<0.01), and decreased markedly in the emodin group compared to the CCl4 group according to METAVIR scale (P<0.01) compared with those in the normal control group (51.02±10.64 IU/L and 132.28±18.14 IU/L). The activities of serum ALT and AST were significantly higher in rats injected with CCl4 (289.25±68.84 IU/L and 423.89±35.67 IU/L, both P<0.05). The activities of serum ALT and AST were significantly reduced by administration of emodin (176.34±47.29 IU/L and 226.1±44.52 IU/L, both P<0.05). Compared with the normal controls (54.53±13.46 mg/g), hepatic hydroxyproline content was significantly higher in rats injected with CCl4 (120.27±28.47 mg/g, P<0.05). Hepatic hydroxyproline content was significantly reduced in the rats treated with emodin at 20 mg/kg (71.25±17.02 mg/g, P<0.05). Emodin signif icantly protected the liver from injury by reducing serum AST and ALT activities and reducing hepatic hydroxyproline content. The mRNA levels of transforming growth factor-β1 (TGF-β1), Smad4 and α-SMA in liver tissues were significantly down-regulated in SD rats that received emodin treatment. Furthermore, significant down-regulation of serum TGF-β1 protein levels and protein expression of Smad4 and α-SMA in liver tissues was also observed in the rats. Emodin inhibited HSC activation by reducing the abundance of TGF-β1 and Smad4.CONCLUSION: Emodin protects the rat liver from CCl4-induced fibrogenesis by inhibiting HSC activation. Emodin might be a therapeutic antifibrotic agent for the treatment of hepatic fibrosis.
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页码:4753 / 4762
页数:10
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