利拉鲁肽对胰岛素抵抗大鼠肾脏NF-κB及炎症因子表达的影响

Effects of liraglutide on the expression of NF kappa-B and inflammatory factor in kidney of insulin resistance rats

目的:探讨利拉鲁肽对胰岛素抵抗大鼠肾组织NF-κB、TNF-α和IL-6表达的影响。方法:将大鼠随机分为4组,对照组(C)、高脂组(H)、利拉鲁肽干预低剂量组[Li-1:100μg/(kg·d)]、利拉鲁肽干预高剂量组[Li-2:200μg/(kg·d)]。用自动生化分析仪检测血肌酐、尿素氮,免疫比浊法测定24 h尿微量白蛋白,用Elisa法测定血清NF-κB、TNF-α及IL-6蛋白的浓度,用RT-PCR法测定肾组织NF-κB、TNF-α及IL-6m RNA的表达。结果 :与对照组相比,高脂组血肌酐、尿素氮、尿蛋白、血清及肾组织NF-κB、TNF-α及IL-6表达均明显升高(P<0.05),电镜可见肾小球基底膜增厚,足突融合;利拉鲁肽高剂量干预可明显减轻这些变化。结论:利拉鲁肽可呈浓度依赖性抑制高脂诱导的胰岛素抵抗大鼠肾脏NF-κB、TNF-α和IL-6的表达,可能参与肾功能改善。

Objective To investigate the effect of liraglutide on the expression of NF-kappa B（NF-KB）, tumor necrosis factor-alpha（TNF-ct） and interleukin-6（IL-6） in renal tissue of insulin resistance rats. Method The rats were divided into 4 groups, control group , high fat group , liraglutide low dose group [ 100μg/（kg·d） ], liraglutide high dose group[ 100μg/（kg·d）]. Detection of serum creatinine and urea nitrogen by automatic biochemical analyzer, and 24 h urine micro albumin was determined by immunoassay. The protein concentration of serum NF-KB,TNF-ct and IL-6 was measured by ELISA. The expression of NF-κB,TNF-ct and IL-6 mRNA in renal tissues was determined by RT-PCR. Results Compared with the control group, the serum creatinine, blood urea nitrogen, urinary protein, and the expression of NF-κB, TNF-ct and IL-6 were significantly higher in high fat group, respectively （P 〈 0.05）. The glomerular basement membrance thickening and foot process fusion were seen under electron microscope. Liraglutide high dose intervention can significantly reduce these changes. Conclusions Liraglutide can inhibit the expression of NF-κB,TNF-α and IL-6 in renal tissues of high fat induced insulin resistance rats,in a concentration dependent manner, which possibly improve renal function.