人工虫草菌丝及其组分对肝纤维化大鼠胆汁酸代谢的影响及其机制研究

Study on effect of artificial CsB and its components on bile acid metabolism in rats with liver fibrosis and its mechanism

胆汁酸是胆固醇在肝中降解的代谢产物,在肝内蓄积可引起肝脏疾病,可造成肝损伤以致肝纤维化。实验采用二甲基亚硝胺(DMN)大鼠肝纤维化模型,分为正常组、模型组和4个给药组。造模4周,给药组分别灌胃给药2周,模型组与正常组同时给予等量灭菌水。实验以血清胆汁酸为标识物,通过检测并观察肝功能指标和胆汁酸代谢的变化,辨识与肝损伤相关的胆汁酸类靶标,首次从胆汁酸代谢水平评价人工虫草菌丝及其组分对肝纤维化大鼠逆转作用并探讨其可能的机制。主要研究内容和结果如下:对牛磺氨酸结合型胆汁酸、甘氨酸结合型胆汁酸和游离型胆汁酸共17种内源性胆汁酸进行了定量分析,结合血清生化指标检测、病理组织切片检查对模型进行了肝损伤评价。造模后ALT,AST活性和TBil含量都显著性升高,Alb含量显著降低。病理组织切片检查HE染色显示模型组正常肝小叶结构破坏,肝细胞水肿,汇管区结缔组织增生,给药组不同程度病理变化减轻。虫草菌丝及其组分可能主要通过激活与HDCA,TCA,TCDCA,TLCA,TUDCA,UDCA,THDCA代谢有关的受体或阻断相关的信号通路而影响大鼠体内胆汁酸的代谢。

Bile acid is a type of metabolite degraded from cholesterol in liver. Its accumulation in liver could cause liver disea- ses, liver damage and liver fibrosis. In this experiment, dimethyl nitrosamine （DMN） liver fibrosis was established in rats. The rats were delivered into the normal group, the model group and four treated groups. After the four-week modeling, the treated groups were orally administered with drugs for 2 weeks, whereas the model and normal groups were given equal amount of sterile water at the same time. In the experiment, serum bile acid was taken the as marker, and liver function indexes and changes in bile acid metabolism were detected and observed to identify liver damage-related bile acid targets. It was the first time to evaluate the reverse effect of artificial CsB and its components on liver fibrosis in rats with bile acid metabolic level, and discuss its potential mechanism. The main study contents and results are as follows： a quantitative analysis was made on totally 17 endogenous bile acids, including taurocholic acid conjugated bile acid, glycine conjugated bile acid and free bile acid, and a liver damage evaluation was made for the model according to the detection of serum biochemical indexes and the pathological biopsy. After modeling, ALT, AST activity and TBil content signifi- cantly increased, whereas Alb significantly decreased. According to the pathological biopsy HE staining, the model group showed dam- age in normal hepatic lobule structure, liver cell edema and connective tissue proliferation in portal area; The treated groups showed mitigation in pathological changes to varying degrees. Cordyceps sinensis and its components may impact the bile acid metabolism in rats by activating HDCA, TCA, TCDCA, TLCA, TUDCA, UDCA, THDCA metabolim-related receptors or blocking relevant signaling pathway.