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[目的]探讨肾气丸对高脂饮食诱导的非酒精性脂肪性肝炎(NASH)大鼠肝细胞脂性凋亡的影响。[方法]采用高脂饲料连续喂养12周建立大鼠NASH模型,40只大鼠随机分为4组,正常组予以标准饲料喂养,其余3组进行高脂饮食造模,除模型组外,其他2组分别以肾气丸、二甲双胍进行干预12周。全自动生化仪检测血脂及血清酶学,ELISA法检测血清游离脂肪酸(FFA)水平;苏木精-伊红染色光镜下观察肝组织病理学变化,计算非酒精性脂肪性肝病(NAFLD)炎症活动度积分(NAS);TUNEL法检测肝细胞凋亡水平,计算凋亡指数(AI)。[结果]NASH模型组大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、FFA水平均较正常组明显增高(P<0.05,<0.01),血清三酰甘油(TG)水平较正常组明显降低(P<0.05),肝组织NAS、AI明显高于正常组(P<0.01)。应用肾气丸和二甲双胍干预后,血清ALT、AST、TC、LDL-C、FFA水平均较模型组明显降低(P<0.05),血中TG、高密度脂蛋白胆固醇(HDL-C)与模型组比较差异无统计学意义(P>0.05)。肝组织NAS和AI较模型组显著降低。相关性分析发现,大鼠肝细胞的AI与肝组织NAS及血清FFA水平呈明显正相关(均P<0.01)。[结论]NASH大鼠存在着脂质代谢紊乱和肝细胞的脂性凋亡。肾气丸与二甲双胍作用相似,可能是通过调节脂质代谢,影响FFA,阻断其引发的促肝细胞脂性凋亡的级联启动,从而有效地防治NASH的进展。
[Objective] To investigate the effect of Shenqi Pill on hepatocellular lipid-induced apoptosis in non-alcoholic steatohepatitis (NASH) rats induced by high-fat diet. [Method] The rat NASH model was established by continuous feeding with high-fat diet for 12 weeks. Forty rats were randomly divided into 4 groups. The normal group was fed with standard diet and the other 3 groups were fed with high-fat diet. Two groups were treated with Shenqi Wan and metformin respectively for 12 weeks. The level of serum free fatty acid (FFA) was measured by ELISA and the pathological changes of liver were observed under hematoxylin-eosin staining, and the inflammation of non-alcoholic fatty liver disease (NAFLD) was calculated Activity score (NAS). TUNEL method was used to detect the level of hepatocyte apoptosis, and the apoptotic index (AI) was calculated. [Results] The levels of serum ALT, AST, TC, LDL-C and FFA in NASH model group were all higher than those in normal group (P <0.05, <0.01). Serum triglyceride (TG) levels were significantly lower than those in the normal control group (P <0.05). The levels of NAS and AI in liver tissues were significantly higher than those in the normal control group (P <0.01). The levels of ALT, AST, TC, LDL-C and FFA in serum were significantly lower than those in the model group (P <0.05) after the intervention of Shenqi Pill and metformin. The levels of TG, HDL- The difference was not statistically significant (P> 0.05). NAS and AI in liver tissue were significantly lower than those in model group. Correlation analysis showed that AI in rat hepatocytes was positively correlated with NAS and serum FFA in liver tissue (all P <0.01). [Conclusion] NASH rats have lipid metabolism disorder and hepatocellular lipid-induced apoptosis. The effect of Shenqi Pill on metformin is similar to that of metformin, which may effectively prevent and cure the progression of NASH by regulating lipid metabolism, affecting FFA and blocking cascade initiation of hepatocellular apoptosis.