七味红花殊胜丸对肝纤维化小鼠Notch/Hes1信号通路的影响

目的： 从Notch/Hes1信号通路探讨七味红花殊胜丸对CCl₄诱导肝纤维化（hepatic fibrosis，HF）小鼠的保护机制。方法： 50只小鼠按照体质量随机分为正常组、模型组、秋水仙碱组、七味红花殊胜丸低、高剂量组，每组10只。模型组、秋水仙碱组、七味红花殊胜丸低、高剂量组小鼠腹腔注射40% CCl₄橄榄油溶液3 mL·kg^-1建立肝纤维化模型，然后七味红花殊胜丸低、高剂量组小鼠分别按3.9 g·kg^-1，7.8 g·kg^-1灌胃七味红花殊胜丸溶液；秋水仙碱组小鼠按0.1 g·kg^-1灌胃秋水仙碱溶液；正常组和模型组小鼠灌胃等量生理盐水，每天1次，连续28 d。末次给药后检测各组小鼠血清ALT、AST水平；观察各组小鼠肝脏病理变化及Notch1、Jagged1、Hes1表达情况。结果： 与模型组比较，七味红花殊胜丸低、高剂量组小鼠血清中ALT、AST活性显著降低（P<0.05）；肝脏组织中Notch1、Jagged1、Hes1基因及蛋白表达显著下降（P<0.05）；HE和Masson染色结果显示，七味红花殊胜丸低、高剂量组小鼠HF得到了不同程度的改善。结论： 七味红花殊胜丸对HF小鼠具有显著的改善作用，其作用机制与调控Notch/Hes1信号通路有关。

Effects of Qiwei Honghua Shusheng Pill on Notch- Hes1 signal pathway in mice with liver fibrosis

OBJECTIVE To explore the protective effects of Qiwei Honghua Shusheng Pill on CCl4-induced liver fibrosis mice and its impact on Notch-Hes1 signal pathway.METHODS A total of 50 healthy mice were randomly divided into four groups of normal, model, colchicine and Qiwei Honghua Shusheng Pill 3.9 g·kg^-1, 7.8 g·kg^-1(n=10 each). And 3 mL·kg^-1 40%CCl4 induced liver fibrosis in model group. Normal saline was injected for normal group. Colchicine group received 0.1 g·kg^-1 colchicine by gastrogavage. Salvianolate group had salvianolate(3.9, 7.8 g·kg^-1) by gastrogavage once daily for 28 consecutive days. The content of ALT/AST, pathological changes and expressions of Notch1, Jagged1 and Hes1 were recorded for each group.RESULTS As compared with model group, Qiwei Honghua Shusheng Pill(3.9, 7.8 g·kg^-1) decreased the content of ALT/AST and the expression levels of Notch1, Jagged1 and Hes1 in liver fibrosis mice(P<0.05). The staining results of HE and Masson indicated that hepatic fibrosis of mice of Qiwei Honghua Shusheng Pill group improved to varying degrees.CONCLUSION Qiwei Honghua Shusheng Pill has the protective effect on liver fibrosis mice induced by CCl4. And its mechanism of action is correlated with the regulation of Notch-Hes1 signal pathway.