消膏转浊方对肥胖型非酒精性脂肪肝大鼠脂质过氧化反应与胰岛素抵抗的影响

Effects of "Xiaogao Zhuanzhuo Decoction" on Lipid Peroxidation and Insulin Resistance in Rats of Obese Non-alcoholic Fatty Liver

目的:观察消膏转浊方对高脂饲养的肥胖大鼠脂质过氧化反应以及胰岛素抵抗(IR)的影响。方法:将Wistar雄性大鼠随机分为正常组、模型组、消膏转浊组、罗格列酮组及饮食控制组。正常组以标准饲料喂养,其余组的大鼠饲以高脂饲料。8周后,正常组饮食同前;模型组继续高脂喂养;消膏转浊组及罗格列酮组改为普通饲料喂养,同时给予相应的药物干预;饮食控制组改为普通饲料喂养。干预12周后,检测大鼠葡萄糖输注率(GIR),肝匀浆中FFA、MDA、SOD的含量,检测肝细胞色素P4502E1的蛋白表达,以及肝脏CYP2E1、胰岛素受体(InsR)和胰岛素受体底物-2(IRS-2)的基因表达。结果:与模型组比较,消膏转浊组可以显著降低大鼠肝组织匀浆中的FFA、MDA含量(P<0.01),同时提高SOD活性(P<0.01);消膏转浊组与罗格列酮组均能够显著提高肥胖型非酒精性脂肪肝大鼠的GIR(P<0.01);消膏转浊组肝细胞中CYP2E1染色阳性的细胞面积和MOD值、CYP2E1 mRNA的表达均显著低于模型组(P<0.01);同时,消膏转浊组与罗格列酮组InsR mRNAI、RS-2 mRNA的表达均显著高于模型组(P<0.01)。结论:高脂饮食可以引起大鼠肝脏脂质过氧化反应以及胰岛素抵抗状态,消膏转浊方可减少肝脏脂质过氧化反应以保护肝脏;同时消膏转浊方通过增加肝脏组织InsR以及IRS-2的表达来改善胰岛素抵抗状态。

Objective： To observe the effects of ＂Xiaogao Zhuanzhuo Decoction＂ on lipid peroxidation and insulin resistance in rats of obese non-alcoholic fatty liver（NAFL）.Methods： The male Wistar rats were randomly divided into 5 groups： normal control group,model group,＂Xiaogao Zhuanzhuo Decoction＂ group,rosiglitazone group and diet control group.The normal control group was fed with ordinary diet;the other groups were fed with high fat diet.After 8 weeks,the diets of the normal control group and model group were not changed,and the diets of the other groups were changed into the ordinary diet.At the same time,the rats of the rosiglitazone group and the ＂Xiaogao Zhuanzhuo Decoction＂ group were treated with the corresponding drugs.Twelve weeks after treatment,the glucose infusion rate（GIR）,the levels of FFA,MDA and SOD in liver homogenate,the protein expression of CYP2E1,and the mRNA expressions of CYP2E1,insulin receptor（InsR） and insulin receptor substrate-2（IRS-2） were detected.Results： Compared with the model group,the levels of FFA and MDA in liver homogenate decreased markedly（P0.01）,and the activity of SOD increased obviously（P0.01） in ＂Xiaogao Zhuanzhuo Decoction＂ group;the GIR of the rats in ＂Xiaogao Zhuanzhuo Decoction＂ group and rosiglitazone group increased significantly（P0.01）;compared with the model group,the positive cell area,the MOD numerus and the mRNA expression of CYP2E1 decreased markedly in ＂Xiaogao Zhuanzhuo Decoction＂ group（P0.01）;meanwhile,the expressions of InsR and IRS-2 mRNA of ＂Xiaogao Zhuanzhuo Decoction＂ group and rosiglitazone group were higher than those of control group（P0.01）.Conclusion： The high fat diet can lead to the action of lipid peroxidation of liver and insulin resistance.＂Xiaogao Zhuanzhuo Decoction＂ has the function of protecting the liver by lessening the action of lipid peroxidation,and meanwhile ＂Xiaogao Zhuanzhuo Decoction＂ can improve the insulin resistance by increasing the expressions of InsR and IRS-2.