目的:基于蛋白磷酸酶(PP1)-DNA依赖的蛋白激酶(DNA-PK)-上游刺激因子1(USF1)信号通路,探讨中药组分HJJB方防治非酒精性脂肪; 肝(NAFLD)的作用机制。方法:采用高脂饮食诱导的大鼠NAFLD模型。设模型组、HJJB方组和罗格列酮组,分别灌胃给药6周。HE染色观察肝组织; 病理变化;测定肝组织甘油三酯(TG)、游离脂肪酸(FFA)含量的变化;肝组织PP1、DNA-PK、USF1; mRNA水平和蛋白含量的变化。结果:模型组肝组织出现显著的肝细胞脂肪变性及空泡样变,肝组织TG、FFA含量较正常组显著升高(P<0.01),肝组; 织PP1、DNA-PK、USF1; mRNA水平和蛋白含量较正常组均明显升高(P<0.01)。HJJB方组的上述病理改变明显减轻,肝组织TG、FFA含量较模型组显著降低(P<0.0; 1),肝组织PP1、DNA-PK、USF1; mRNA水平和蛋白含量较模型组显著降低(P<0.01)。结论:HJJB方能显著降低脂肪肝大鼠肝组织PP1; mRNA水平和蛋白含量,进而抑制其下游信号通路,这可能是其防治NAFLD的重要机制。Objective: Toexplore the mechanism of Chinese herb component HJJB; Compound on non-alcoholic fatty liver disease based on PP1-DNA-PK-USF1; signaling pathway. Methods: SD male rats were induced by high-fat diet; for nonalcoholic fatty liver disease model. The rats were randomly; divided into model group, HJJB group and rosiglitazone group, and were; given intragastric administration for six weeks. The observing items; including: liver pathology(HE staining); hepatic triglyceride(TG) and; free fatty acid(FFA) content; mRNA and protein content changes of; hepatic protein phosphatase 1(PP1), DNA-dependent protein kinase(DNA-PK); and upstream stimulating factor 1(USF1). Results: Significant hepatocyte; fatty degeneration and vesicle changes were observed in liver tissue of; model group. The hepatic TG and FFA contents of model group were; significantly higher than those of normal group(P<0.01), and mRNA levels; and protein contents of liver tissue PP1, DNAPK, USF1 in model group; were significantly higher than those in normal group(P<0.01). Hepatic; pathological changes in HJJB Compound group were meliorated, liver; tissue TG and FFA contents of HJJB Compound group were significantly; lower than those of model group(P<0.01), and mRNA levels and protein; contents of liver tissue PP1, DNA-PK, USF1 mRNA of HJJB Compound group; were significantly lower than those of model group(P<0.01). Conclusion:; HJJB Compound can significantly decrease mRNA level and protein content; of PP1 in the liver tissue of fatty liver rats, and then inhibit the; downstream signaling pathway of PP1, which may be an important mechanism; of HJJB Compound for prevention and treatment of non-alcoholic fatty; liver disease.国家自然科学基金项目; 浙江省自然科学基金项目; 浙江省中医药科技计划项
