Emodin protects rat liver from CCl_4-induced fibrogenesis via inhibition of hepatic stellate cells activation  

作　　者：Miao-Xian Dong Yan Jia Ying-Bo Zhang Cheng-Chong Li Yu-Tao Geng Li Zhou Xue-Yan Li Ji-Cheng Liu Ying-Cai Niu 

机构地区：[1]The Institute of Medicine, Qiqihar Medical University, Qiqihar161042, Heilongjiang Province, China [2]Department of Pathophysiology, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China

出　　处：《World Journal of Gastroenterology》2009年第38期4753-4762,共10页世界胃肠病学杂志（英文版）

基　　金：Supported by National Natural Science Foundation of China,No.30873396;National Science Foundation for Post-doctoral Scientists of China,No.20080430140;Qiqihar Foundation for Development of Science and Technology,China,No.05090

摘　　要：AIM： To investigate the role of emodin in protecting the liver against fibrogenesis caused by carbon tetrachloride （CCh） in rats and to further explore the underlying mechanisms. METHODS： Rat models of experimental hepatic fibrosis were established by injection with CCh; 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）, immunohistochernistry, western blotting and enzymelinked immunosorbent assay.RESULTS： The degree of hepatic fibrosis increased markedly in the CCh group compared to the normal group （P 〈 0.01）, and decreased markedly in the emodin group compared to the CCI4 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 CCh （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 CCI4 （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 significantly protected the liver from injury by reducing serum AST and ALT activities and reducing hepaAIM: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 an

关 键 词：EMODIN Hepatic fibrosis Transforming growth factor-β1 SMAD4 Hepatic stellate cell α-smooth muscle actin 

分 类 号：R575[医药卫生—消化系统]