姜黄素治疗肝纤维化与肝星状细胞的关系

The study of therapeutic effect of curcumin on hepatic fibrosis and its relationship with hepatic stellate cells

目的观察姜黄素治疗大鼠肝纤维化中活化肝星状细胞(hepatic stellate cell,HSC)的数目、分布、凋亡等变化,探讨两者间的关系。方法以四氯化碳(CCl4)腹腔注射的方法制作大鼠肝纤维化模型,姜黄素治疗组于第9周起分别予姜黄素10、20、40 mg/100 g体质量灌胃,设立正常组、溶剂组、模型组和丹参组,14周后处死大鼠,留取肝左叶行HE和Masson胶原染色,光镜下观察病理学改变,并按SSS计分系统进行肝纤维化程度评分,免疫组化方法检测α-SMA,TUNEL与Desmin免疫组化双染法检测HSC凋亡。结果与模型组比较,姜黄素组能明显改善CCl4所致大鼠肝纤维化的病理学改变,肝纤维化评分明显降低(P<0.05),接近正常组。与正常组比较,模型组活化HSC明显增多,而极少发生凋亡,姜黄素可以明显减少活化HSC数量并增加其凋亡率(P<0.05);上述作用随姜黄素剂量的增加而增强。结论姜黄素可抑制HSC活化、增殖,诱导HSC凋亡,姜黄素可能通过上述机制发挥治疗肝纤维化的作用。

Objective To investigate therapeutic effect of curcumin on hepatic fibrosis and the number,location and apoptosis of activated hepatic stellate cell（ HSC） in the liver,and discuss the relationship between the therapeutic effects and the HSC. Methods Rat models of hepatic fibrosis were made by carbon tetrachloride（ CCl4）. Curcumin of10 mg,20 mg,40 mg per 100 gram weight of rat were given to these rats of curcumin groups respectively from ninth week. Normal group,dissolvent group,model group and Salvia miltiorrhiza group were made as controls. After 14 weeks,all rats were executed and left livers were extirpated for pathologic examination including HE and Masson staining. HE and Masson staining were conducted in hepatic tissues to observe pathological variations. Grades of hepatic fibrosis were evaluated according to the SSS system. Activated HSC was detected by α-SMA immuohistochemistry staining. HSC apoptosis was detected by double-stain of terminal deoxynucleotidyl transferase（ Td T） d UTP nickend labeling（ TUNEL） and Desmin immuohistochemistry staining,and professional software for image analysis was used. Results Compared with model group,curcumin could obviously improve liver pathological variations of fibrotic rats. The score of hepatic fibrosis in curcumin group reduced significantly（ P〈0. 05）. Aactivated HSC increased significantly in fibrotic group compared with that of normal group,and few apoptotic HSC were detected. However,less activated HSC and more apoptotic HSC were detected in curcumin treated groups compared with fibrotic group. These effects were dose-dependent. Conclusion Curcumin could inhibit activation and proliferation of HSC,and induce apoptosis of HSC,which may be contribute to the therapeutic effects of curcumin on hepatic fibrosis.