IKKε在糖尿病大鼠肝脏的表达及利拉鲁肽对其干预作用的研究

Expression of IKKε in liver of diabetic rats and the effect of Liraglutide on the expression

目的观察糖尿病大鼠肝脏组织IKKε、核因子κB(NF-κB)、磷酸化蛋白激酶B(p-Akt)的表达及利拉鲁肽对其干预的作用。方法采用高脂饮食联合STZ诱导建立T2DM大鼠模型,将成模大鼠随机分为糖尿病组(T2DM)、低剂量利拉鲁肽组(LL)、高剂量利拉鲁肽组(HL),另设正常对照组(NC),每组各10只。Western blot检测肝脏组织IKKε、NF-κB、p-Akt的蛋白表达,RT-PCR检测IKKε、NF-κB的mRNA表达。结果 T2DM组FPG、FIns、HOMA-IR、TG、白介素6(IL-6)、丙二醛(MDA)较NC组、LL组、HL组高(P<0.05或P<0.01),HL组FPG、FIns、IL-6、MDA、HOMA-IR较LL组低(P<0.05)。与NC组比较,HL组、LL组、T2DM组IKKε、NF-κB的蛋白表达依次升高(P<0.05或P<0.01),p-Akt的蛋白表达依次降低[(0.762±0.112)vs(0.598±0.085)vs(0.476±0.112)vs(0.342±0.097),P<0.05或P<0.01]。结论肝脏组织IKKε表达升高可能参与了糖尿病的发生,利拉鲁肽呈浓度依赖下调肝脏组织IKKε的表达,可能是其改善IR、糖代谢的部分机制。

Objective To observe the expressions of IKKε,NF-κB and p-Akt in the liver tissues of diabetic rats and the their changes under intervention of Liraglutide. Methods The rat model of diabetes mellitus （DM） was established by intravenous injection of streptozotocin （STZ）after 4-week high fat diet.The diabetic rats were randomly divided into diabetes （T2DM）group,Liraglutide low dose group （LL） and Liraglutide high dose group （HL）.The normal rats served as control group （NC）.There were 10 rats in each group.Western blot assay was adopted to detect the protein expressions of IKKε,NF-κB and p-Akt.RT-PCR was used to detect the mRNA expressions of IKKεand NF-κB. Results The levels of FPG,FIns,HOMA-IR,TG,IL-6,and malondialdehyde （MDA）were significantly higher in DM group than those in NC group,LL group and HL group （P〈0.05 or P〈0.01）.Compared with LL group,the levels of FPG,FIns,IL-6,MDA and HOMA-IR were decreased in HL group （P〈0.05）.Compared with NC group,the expressions of IKKεand NF-κB in liver tissue increased gradually in HL group,LL group and T2DM group （P〈0.05 or P〈0.01）.Compared with NC group,the expressions of p-Akt in liver tissue decreased gradually in HL group,LL group and T2DM group[ （0.762±0.112）vs （0.598±0.085）vs （0.476±0.112）vs （0.342±0.097）,P〈0.05 or P〈0.01]. Conclusion Increased expression of IKKεin liver tissue may be involved in the development of diabetes.Liraglutide down-regulates the expression of IKKεin a concentration-dependent manner,which may be part of its mechanism to improve IR and glucose metabolism.