大黄素介导IRS-2/PI3K/Akt通路干预大鼠非酒精性脂肪性肝炎的实验研究

目的探讨大黄素通过介导IRS-2/PI3 K/Akt通路对非酒精性脂肪性肝炎(NASH)的影响。方法随机选取25只雄性大鼠给予高脂饲料喂养12周制备NASH模型,12周后取5只大鼠进行检测,确定NASH模型制备成功,剩余20只大鼠数字表法随机分为模型组(10只)和大黄素组(10只),另取同龄10只雄性未造模大鼠作为正常对照组。大黄素组大鼠给予20 mg/kg的大黄素灌胃,正常对照组和模型组给予等量生理盐水,连续给予8周。对大鼠肝脏进行称重,计算肝指数;检测空腹血糖和空腹胰岛素,计算胰岛素抵抗指数(HOMA-IR),检测血生化指标。对肝组织进行HE染色,检测肝组织中IRS-2、p-IRS-2、PI3K、p-PI3K、Akt、p-Akt蛋白相对表达量。结果模型组大鼠肝指数、空腹血糖、空腹胰岛素、HOMA-IR、ALT、AST、TG、TC和LDL-C水平较正常对照组增高,HDL-C水平较正常对照组降低(P<0.01);大黄素组大鼠肝指数、空腹血糖、空腹胰岛素、HOMA-IR、ALT、AST、TG、TC和LDL-C水平较模型组降低,HDL-C水平较模型组增高(P<0.05)病理检测发现,模型组出现大量脂肪变性,存在炎性细胞浸润和细胞气球样变性,大黄素组病灶明显较模型组减轻。模型组大鼠IRS-2、p-IRS-2、PI3K、p-PI3K、Akt、p-Akt蛋白相对表达量较正常对照组降低(P<0.05),大黄素组大鼠IRS-2、p-IRS-2、PI3K、p-PI3K、Akt、p-Akt蛋白相对表达量较模型组增高(P<0.05)。结论大黄素可以提高IRS-2/PI3K/Akt通路的活性,改善高脂诱导的NASH大鼠肝脏脂肪沉积及胰岛素抵抗。

The experimental study of emodin mediated IRS-2/PI3K/Akt pathway on nonalcoholic steatohepatitis in rats

Objective To investigate the effect of emodin on nonalcoholic steatohepatitis(NASH) through IRS-2/PI3 K/Akt pathway.Methods Twenty-five male rats were randomly fed with high fat diet for 12 weeks.After 12 weeks,5 rats were taken for detection.The remaining 20 rats were randomly divided into model group(10 rats) and emodin group(10 rats).Another 10 male non model rats of the same age were taken as the normal control group.Rats in emodin group were given 20 mg/kg emodin by gavage.Normal control group and model group were given the same amount of normal saline for 8 weeks.The rat liver was weighed and the liver index was calculated.Fasting blood glucose and fasting insulin were measured,insulin resistance index(HOMA-IR) was calculated,and biochemical indexes were measured.He staining was used to detect the relative expression of IRS-2,p-IRS-2,PI3 K,p-PI3 k,Akt and p-Akt in liver tissue.Results The liver index,fasting blood glucose,fasting insulin,HOMA-IR,ALT,AST,TG,TC and LDL-C levels in the model group were higher than those in the normal control group,and the HDL C level was lower than that in the normal control group(P <0.01).The liver index,fasting blood glucose,fasting insulin,HOMA-IR,ALT,AST,TG,TC and LDL-C levels in the emodin group were lower than those in the model group,and the HDL-C level was higher than the model group(P <0.05).Pathological examination revealed that there was a large amount of steatosis in the model group,inflammatory cell infiltration and balloon-like degeneration,and the lesions in the emodin group were significantly less than those in the model group.The relative expression levels of IRS-2,p-IRS-2,PI3 K,p-PI3 K,Akt and p-Akt in the model group were lower than those in the normal control group(P <0.05),and in the emodin group IRS 2,p IRS 2,PI3 K,p PI3 K The relative expression of Akt and p Akt protein was higher than that of the model group(P <0.05).Conclusion Emodin can enhance the activity of IRS-2/PI3 K/Akt pathway,improve the fatty deposition and insulin resistance of Nash rats induced by high fat.