胰高血糖素样肽-1通过抑制NF-κB信号通路减轻白介素-1β诱导的INS-1细胞损伤  

Glucagon-like peptide-1 protects INS-1 cells from interleukin-1β-induced damage by inhibiting the nuclear factor-κB pathway

作　　者：李圣坚[1] 薛耀明[1] 李佳[1] 朱波[1] 张巧玲[1] 陈毅光[1] 

机构地区：[1]南方医科大学南方医院内分泌科,广东广州510515

出　　处：《南方医科大学学报》2010年第9期2119-2121,2124,共4页Journal of Southern Medical University

基　　金：广东省科技计划项目(2009B08701020);广东省中医药局科研课题(2009454)

摘　　要：目的探讨胰高血糖素样肽-1(GLP-1)对白介素-1β(IL-1β)诱导INS-1细胞损伤的影响及其可能机制。方法体外培养大鼠胰岛素瘤细胞株细胞(INS-1)至对数生长期,根据干预方案进行分组:正常对照组、IL-1β组、GLP-1+IL-1β组。采用MTT法观察细胞活力、荧光实时定量PCR检测细胞内IKKβmRNA水平的表达,免疫印迹法(Western blotting)检测转入细胞核内NF-κB p65亚基的蛋白水平。结果与对照组相比,IL-1β组细胞活力下降29%,差异具有统计学意义(P<0.001);当加入GLP-1预处理后,细胞活力上升了30%,差异具有统计学意义(P<0.001)。与对照组相比,IL-1β组的IKKβmRNA表达显著增加(1.967±0.091vs1±0);当加入GLP-1预处理后,与IL-1β组相比,GLP-1+IL-1β组的IKKβmRNA表达显著降低(1.967±0.091vs1.287±0.084)。与对照组相比,IL-1β组核内NF-κB蛋白水平显著增高(0.814±0.111vs0.396±0.026);而加入GLP-1预处理后,与IL-1β组相比,GLP-1+IL-1β组核内NF-κB蛋白水平显著减少(0.622±0.059vs0.814±0.111)。结论 GLP-1抑制IL-1β诱导的INS-1细胞损伤,其机制可能与其抑制NF-κB信号通路有关。Objective To observe the effect of glucagon-like peptide-1（GLP-1） on interleukin-1β（IL-1β）-induced damage in INS-1 cells and explore its possible mechanisms.Methods INS-1 cells were divided into normal control group,IL-1β group,and GLP-1＋IL-1β group with correaponding treatments.The cell viability was determined by MTT assay,the expression of IKKβ mRNA was detected by real-time PCR,and that of the protein p65 was detected by Western blotting.Results In comparison with the normal control group,the cells in the IL-1β group showed a significantly decreased viability by 29%（P〈0.01）;compared with those in IL-1β group,the cells in GLP-1＋IL-1β group exhibited an significant increase in the cell viability by 30%（P〈0.01）.In comparison with the normal control group,the cells in IL-1β group showed an significantly increased expression of IKKβ mRNA（1.967±0.091 vs 1±0,P〈0.05）;GLP-1 significantly reduced IL-1β-induced increment of IKKβ mRNA expression to 1.287±0.084（P〈0.05）.IL-1β treatment significantly increased NF-κB protein expression as compared to the control level（0.814 ±0.111 vs 0.396±0.026,P〈0.01）,and GLP-1 significantly inhibited such effect（0.622± 0.059,P〈0.05）.Conclusions GLP-1 inhibits IL-1β-induced β-cell damage probably by inhibiting the NF-κB pathway.

关 键 词：胰高血糖素样肽-1 白介素-1Β 核因子-KB IkB激酶β INS-1 

分 类 号：R587.1[医药卫生—内分泌]