糖耐康改善KKAy小鼠Toll样受体4通路及葡萄糖转运子4的作用机制研究

Mechanism of Tangnai Kang in Improving TLR4 Signaling Pathway and GluT-4 in KKAy Diabetic Mice

目的:观察中药糖耐康对KKAy小鼠血糖、体质量及Toll样受体4(TLR4)通路中白细胞介素6(IL-6)、核因子κB激酶β抑制物(IKKβ)及葡萄糖转运蛋白4(GluT4)影响,分析其改善2型糖尿病的可能作用机制。方法:选取无特定病原体(SPF)级自发性2型糖尿病动物KKAy小鼠及C57BL/6J小鼠,给予高脂饲料喂养,连续8周给药,评价血糖及体质量。并采用半定量酶联免疫吸附测定(ELISA)检测血浆中IL-6及GluT4的水平。蛋白质印迹法检测肝组织TLR4蛋白表达、肌肉组织IKKβ蛋白表达水平。结果:中药糖耐康高剂量组,能够显著降低血糖水平(P<0.05),具有一定抑制体质量增长的趋势。同时能够下调IL-6水平,上调GluT4的水平(P<0.01,P<0.05),抑制TLR4及IKKβ蛋白表达(P<0.01,P<0.05)。结论:糖耐康可能通过下调脂多糖(LPS)介导的TLR4通路中关键炎症介质的水平,减轻低度炎症反应,在一定程度上抑制炎症级联效应,同时提高胰岛素信号转导受体后途径中GluT4的转位及活性水平,共同达到改善胰岛素抵抗状态的作用。

Objective:To observe the effects of traditional Chinese medicine(TCM)compound Tangnai Kang on blood sugar,body weight,interleukin-6(IL-6)and inhibitor of nuclear factor kappaB kinase beta(IKKβ)in Toll-like receptor 4(TLR4)signaling pathway and glucose transporter 4(GluT-4)in KKAy mice,and to discuss its possible mechanism in improving type 2 diabetes mellitus(T2DM).Methods:SPF KKAy and C57BL/6J mice(spontaneous T2DM animals)were selected and fed with high fat food.After 8 weeks,blood sugar and body weight were evaluated and the levels of IL-6 and GluT-4 in plasma were measured by semi-quantitative ELISA.The protein expressions of TLR4 in liver tissue and IKKβin muscle tissue were detected by Western blot.Results:High dose of Tangnai Kang reduced blood glucose(P<0.05)and controlled the growth trend of body weight.It also decreased the level of IL-6 and increased the level of GluT-4(P<0.01,P<0.05),and inhibited the protein expressions of TLR4 in liver tissue and IKKβin muscle tissue(P<0.01,P<0.05).Conclusion:Tangnai Kang may reduce the low-grade inflammation response by down-regulating the key inflammatory factors in the LPS-mediated TLR4 signaling pathway,and thus inhibit the inflammatory cascade effect to some extent.It also enhances the transposition and activity of GluT-4 in the insulin signal transduction pathway,to jointly improve the insulin resistance.