津力达对高脂诱导的胰岛素抵抗ApoE^(-/-)小鼠MAPK信号通路的影响

Effect of Jinlida on MAPK signaling pathways in skeletal muscle in ApoE^(-/-) mice with fat-induced insulin resistance

目的:探究津力达对高脂诱导的胰岛素抵抗Apo E-/-小鼠丝裂原活化蛋白激酶(MAPK)信号通路的影响。方法:8只雄性C57BL/6J小鼠设为正常组(NF)、40只雄性Apo E-/-小鼠喂养16周后分为模型组(HF)、罗格列酮组(LGLT)、津力达低剂量组(JLDL)、津力达中剂量组(JLDM)、津力达高剂量组(JLDH),开始灌胃(ig)给药,连续8周。采用放射免疫法测定小鼠血清水平胰岛素水平;组织游离脂肪酸试剂盒小鼠骨骼肌游离脂肪酸(FFA)含量;葡萄糖耐量实验(OGTT)评价小鼠的胰岛素抵抗程度;苏木精-伊红染色(HE)光镜下观察小鼠骨骼肌细胞器改变;电镜超微结构观察小鼠骨骼肌改变;蛋白质印迹法(Western Blot)测定小鼠骨骼肌MAPK通路相关酶蛋白表达。结果:津力达能够不同程度降低小鼠的空腹血糖(FBG)、胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C),升高高密度脂蛋白(HDL-C);不同程度下调小鼠骨骼肌游离脂肪酸(FFA)含量;下调空腹胰岛素(FIns)、胰岛素抵抗指数(HOMA-IR),明显改善小鼠糖耐量异常;下调小鼠骨骼肌p-P38的蛋白含量。结论:津力达可能能够通过抑制骨骼肌p38的磷酸化,阻断MAPK信号通路,改善高脂诱导的Apo E-/-小鼠的胰岛素抵抗。

Objective： To investigate the effect of Jinlida on the MAPK signaling pathway in Apo E^- /-mice with insulin resistance induced by high-fat. Methods： Eight male C57 BL /6J mice were used as the normal control.Forty male Apo E^- /-mice were fed with high fat for sixteen weeks,and then divided into 5 groups and treated with oral rosiglitazone（ LGLT） and Jinlida low dose group（ JLDL）,Jinlida middle dose group（ JLDM）,Jinlida highdose group（ JLDH）,began gavage for eight weeks. Serum insulin was measured by radioimmunoassay,free fatty acid in skeletal muscle was detected using a kit,and insulin resistance was evaluated by glucose tolerance test. Theexpression of MAPK pathway-related enzymes in skeletal muscle was detected by Western blotting. Results： Jinlida reduced fasting blood glucose（ FBG）,cholesterol（ TC）,triglyceride（ TG） and low density lipoprotein cholesterol（ LDL-C） to varying degrees,and increased high density lipoprotein（ HDL-C）. It also reduced FFA content in skeletal muscle,fasting insulin（ FIns） levels and insulin sensitive index（ ISI）,and significantly improved abnormal glucose tolerance in mice. Western blotting results showed the down-regulation of phosphorylated p38 level in skeletal muscle. Conclusion： Jinlida improves insulin resistance induced by high fat in Apo E^- /-mice,which may be duo to inhibition of p38 phosphorylation in skeletal muscle and the MAPK signal pathway.