三七总皂苷调控c-Jun氨基末端激酶改善大鼠肝组织胰岛素抵抗的作用

目的构建高脂高胆固醇饮食诱导胰岛素抵抗SD大鼠模型,探讨三七总皂苷改善胰岛素抵抗的作用及其机制.方法 Sprague-Dawley(SD)雄性大鼠60只,随机分为对照组、模型组和治疗组.对照组喂以普通饮食,模型组和治疗组以高脂高胆固醇灌胃加普通饮食喂养16周诱发胰岛素抵抗(IR)后,治疗组给予三七总皂苷治疗8周,2组大鼠继续高脂高胆固醇灌胃直到24周取材.用化学比色法检测3组大鼠肝组织氧化应激相关酶和产物:谷胱甘肽(GSH)、谷胱甘肽还原酶(GR)、丙二醛(MDA)和总超氧化物歧化酶(T-SOD)活力;Western blotting检测3组大鼠肝组织中丝裂原活化蛋白激酶(MAPKs)家族的c-Jun氨基末端激酶(JNK)活性变化.结果模型组体重、Lee’s指数、甘油三酯、总胆固醇、游离脂肪酸、血胰岛素和胰岛素抵抗指数明显高于对照组(P<0.05);内源性巯醇抗氧化剂(酶)GSH和GR含量减少,MDA的含量明显升高,JNK激酶磷酸化增高;三七总皂苷治疗8周后大鼠高脂血症和胰岛素抵抗明显改善;抑制JNK激酶磷酸化.但空腹血糖在3组间没有差异(P>0.05).结论三七总皂苷能减轻胰岛素抵抗模型大鼠高脂血症,上调大鼠肝组织中内源性巯醇抗氧化物(酶)GSH和GR含量,抑制应激蛋白激酶JNK活性,改善大鼠肝组织胰岛素抵抗.

Panax Notoginseng Saponin Regulates c-Jun N-terminal Kinase to Improve Insulin Resistance of Rat Liver Tissue

Objective To study the effect and mechanism of Panax Notoginseng Saponin(PNS) in attenuating insulin-resistance by exploiting insulin-resistant SD rats induced by high-fat and high-cholesterol diet.Methods 60 Sprague-Dawley(SD)male rats were randomly divided into three groups:control group(20 rats),model group(20 rats)and treatment group(20 rats).The rats in control group were fed with normal diet.By contrast,the rats in model group and the treatment group(20 rats) were intragastricly administrated with high fat and high cholesterol besides normal diet for 16 weeks to induce insulin resistance.The rats in treatment group were further intragastricly administrated with TPNS for 8 weeks.The rats in the two groups were intragastricly administrated with high fat and high cholestero until 24 weeks.MDA,GSH,GR and T-SOD in liver tissues were measured by chemical colorimetric analysis.And the c-Jun N-terminal kinase were determined by Western blotting.Results Triglyceride,total cholesterol,free fatty acid,insulin and insulin resistance index(IRI)of rats in the model group were significantly higher than in the control group(P<0.05).The MDA of rats in model group was significant higher than in the control group(P<0.05);the activities of GSH and GR of rats in model group were significantly lower than in the control group(P<0.05).There was no significant difference(P>0.05)in T-SOD among three groups.JNK phosphorylation increased in liver tissue of insulin-resistant model rats.After treatment of TPNS,hyperlipidemia and insulin resistance in rats in the treatment group were significantly attenuated(P<0.05).PNS treatment reversed the process of phosphorylation of the above proteins.Conclusions PNS can attenuate hyperlipidemia of rats with insulin resistance and by increasing endogenous thiol antioxidant(enzyme) GSH,GR,level to protect liver tissue.At molecular level,PNS can attenuate insulin resistance by decreasing the activities of JNK in the insulin signaling pathway.