ak/Stat信号通路在经典CCl4大鼠肝纤维化模型中的动态变化及扶正化瘀方对其影响

ObjectiveTo investigate the role of Jak/Stat pathway in the CCl4-induced rat liver fibrosis model and the molecular action mechanism of Fuzheng Huayu recipe in the treatment of liver fibrosis. MethodsExperimental rats were randomly divided into control group, CCl4-induced liver fibrosis model group (model group), and Fuzheng Huayu recipe group (FZHY group). Blood and liver tissue samples were collected at different time points during fibrosis development, reversion, and intervention. Serum levels of alanine aminotransferase (ALT) and hyaluronic acid (HA) were determined by Olympus AU2700 automatic biochemical analyzer and radioimmunoassay, respectively. The degree of liver fibrosis was evaluated by the Ishak score system. The protein expression of alpha-smooth muscle actin (α-SMA) was measured by immunohistochemistry. The mRNA and protein expression of Jak1 and Stat3 was measured by RT-PCR and Western-Blot, respectively. Comparison between groups was made by one-way analysis of variance. ResultsDuring treatment with CCl4, the model group had increasing liver tissue inflammation and fibrosis, as well as elevated protein expression of α-SMA and mRNA and protein expression of Jak1 and Stat3, and these indices reached the peak levels at week 8; later, the rats showed improvements in liver tissue inflammation and fibrosis and significant decreases in the above indices after CCl4 were discontinued. At weeks 4, 6, and 8, the FZHY group had significantly decreased serum levels of ALT and HA, significantly reduced liver tissue inflammation and fibrosis, and significantly down-regulated mRNA and protein expression of Jak1 and Stat3, as compared with the model group. ConclusionThe Jak/Stat pathway plays an important role in the development and reversion of liver fibrosis. Fuzheng Huayu recipe can reduce liver fibrosis by blocking the Jak/Stat pathway and inhibiting activation of hepatic stellate cells