摘要
[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 observe lipids apoptosis in the liver tissues of rats with nonalcoholic steatosishepatitis（NASH）induced by high-fat diet, and the effect of Shenqi pill. [Methods]The rat model of NASH was induced by 12-week high-fat diet,and treated with Shenqi pill and metformin. Serum ALT,AST,TG,CHO, HDL,LDL and TG,CHOL of liver homogenate were examined by biochemical method. Contents of serum FFA were examined by ELISA. Pathological changes of liver were detected by HE. NAFLD activity score was calculated. Hepatocyte apoptosis was observed by TUNEL method and hepatocyte apoptosis index was accounted accordingly. [Results] NAS in NASH model group was remarkably higher than that in the control group （P〈0.01） ;and those in Shenqi pill group and metformin group were significantly reduced as compared with the model group（P〈0.01, P〈0.05）. Serum ALT, AST, CHOL, LDL, FFA, and TG, CHOL of liver homogenate in the model group were remarkably higher than those in the control group （P〈 0.01, P〈0.05）. The model group and the control group showed no significant difference between serum HDL（P〈0.05）. Serum ALT, AST, CHOL, HDL, FFA and TG, CHOL of liver homoge- nate in the Shenqi pill group and metformin group were significantly reduced as compared with those in the model group（P〈0. 05）. Hepatocyte apoptosis of the model group was remarkably higher than that in the normal group（P〈0. 01）;while hepatocyte apoptosis in Shenqi pill group and metformin group was significantly reduced（P〈0. 05）. There was a positive correlation be- tween hepatocyte apoptosis index and the degree of liver NASH activity score or FFA level（r〈 0. 946,0. 500,both P〈0.01）. [Conclusion] Hepatocyte lipid apoptosis existed in the NASH rats induced by high-fat diet. With the effect on FFA, Shenqi pill may resist lipid peroxidization, thus block initiations of cascades starts of promoting liver lipid apoptosis,and prevent the further development of NASH.
出处
《中国中西医结合消化杂志》
CAS
2011年第6期366-369,共4页
Chinese Journal of Integrated Traditional and Western Medicine on Digestion
基金
浙江省自然科学基金资助项目(Y2100170)
关键词
肝炎
非酒精性
脂肪性
脂性凋亡
肾气丸
nonalcoholic steatohepatitis
lipid apoptosis
Shenqi pill
