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Action mechanism of Yi Guan Jian Decoction on CCl₄ induced cirrhosis in rats

Mu, Yongping, Liu, Ping, Du, Guangli, Du, Jinxing, Wang, Gaoqiang, Long, Aihua, Wang, Lei, Li, Fenghua
Journal of ethnopharmacology 2009 v.121 no.1 pp. 35-42
Oriental traditional medicine, herbal medicines, medicinal properties, liver cirrhosis, rats, animal disease models, carbon tetrachloride, fibrosis, histopathology, hepatocytes, apoptosis, metalloproteinases
Aim of study: To investigate action mechanism of Yi Guan Jian Decoction on cirrhosis induced by CCl₄ in rats. Material and methods: CCl₄ (3mL/kg) for the first time and then olive oil CCl₄ solution 50% (2mL/kg) was administered hypodermically to rats twice each week for 12 weeks. At the end of 8th week, rats were randomly divided into CCl₄ control group (n =10), Yi Guan Jian Decoction group (n =9) and Xiao Chai Hu Decoction group (n =9). Yi Guan Jian Decoction and Xiao Chai Hu Decoction were oral administrated per day respectively for 4 weeks, concomitantly continued CCl₄ administration. At 12th weekend, the rats were sacrificed for sampling and detection of liver function, histological changes of liver tissue, liver tissue hydroxyproline content and expression of α-SMA, CD68, MMP-13, TIMP-1, TIMP-2, Caspase-12, HGFα, MMP-2, MMP-9 and hepatocyte apoptotic index. Results and conclusions: (1) Compared with that of normal rats, expression of α-SMA, CD68 and TIMP-1 in liver tissue of 8 week model group rats increases significantly (P <0.01), moreover further increased in the 12 week of model group. However, MMP-13, HGFα, TIMP-2 content decreases gradually and the statistical difference is seen between each time point (P <0.01). Activity of MMP-2, MMP-9, content of Caspase-12 and hepatocyte apoptotic index increased gradually at 4th, 8th, 12th week. (2) Compared to that of the same time point model group, activity of MMP-9 and contents of MMP-13, TIMP-2 and HGFα in Yi Guan Jian Decoction group improves significantly (P < 0.01), and activity of MMP-2 and contents of α-SMA, TIMP-1, Caspase-12 and hepatocyte apoptotic index decreases significantly (P < 0.01). This work suggests that Yi Guan Jian Decoction exerts significant therapeutic effect on CCl₄-induced cirrhosis in rats, through mechanism of inhibiting hepatocytes apoptosis and hepatic stellate cells activation, and regulating the function of Kupffer cell. Ethnopharmacological relevance: This study investigates the mechanism of Yi Guan Jian against cirrhosis from aspect of heptocytes apoptosis and hepatic stellate cells activation. It suggest that although of unknown bioactive ingredients, mechanism of traditional Chinese medicine recipe against cirrhosis can be disclosed and of profound significance.