摘要
目的:观察GLP-1对糖尿病小鼠中Par-4/NF-κB的表达和胰岛β细胞凋亡的影响。方法:将小鼠随机分成正常对照组(8只,C组)、Par-4敲除组(8只,CP组)、糖尿病组(8只,D组)、糖尿病Par-4敲除组(8只,DP组)、GLP-1+糖尿病组(8只,GD组)、GLP-1+糖尿病Par-4敲除组(8只,GDP组),TUNEL法检测各组细胞凋亡,Western blot检测各组细胞Par-4和NF-κB蛋白表达水平,ELISA检测各组胰岛素分泌。结果:C组凋亡率(P=0.965)和NF-κB(P=0.754)与CP组比较无统计学差异,胰岛素分泌无统计学差异(P=0.797);与C组和CP组比较,D组凋亡率(P=0.000)、Par-4(P=0.000)和NF-κB(P=0.000)表达明显升高,胰岛素分泌下降(P=0.000);与D组相比,DP组和GD组细胞凋亡率(P=0.000,P=0.000)、Par-4(P=0.000,P=0.000)和NF-κB(P=0.000,P=0.002)表达明显下降,胰岛素分泌有所改善(P=0.000,P=0.026);与GD组比较,GDP组凋亡率(P=0.000)、Par-4(P=0.000)和NF-κB(P=0.015)表达明显下降,胰岛素分泌有所改善(P=0.026),DP组和GDP组在凋亡率(P=0.930)、Par-4(P=0.965)和NF-κB(P=0.875)表达及胰岛素分泌(P=0.797)方面无统计学差异。结论:GLP-1干预通过抑制Par-4/NF-κB表达,改善2型糖尿病胰岛β细胞凋亡和胰岛素分泌功能。
Objective:To observe the effect of glucagon-like peptide-1(GLP-1)on the expression of Par-4/NF-κB and the apoptosis of isletβcells in diabetic mice.Methods:Experimental mice were randomly divided into normal control group(C group),Par-4 knockout group(CP group),diabetes group(D group),diabetes and Par-4 knockout group(DP group),GLP-1+diabetes group(GD group),and GLP-1+diabetes and Par-4 knockout group(GDP group),with 8 mice in each group.For each group,the apoptosis rate of isletβcells was determined by TUNEL assay,the protein expression levels of Par-4 and NF-κB were determined by Western blot,and insulin secretion was measured by ELISA.Results:There were no significant differences between the CP group and the C group in the apoptosis rate of isletβcells(P=0.965),NF-κB expression(P=0.754),and insulin secretion(P=0.797).Compared with the C group and CP group,the D group had significantly increased apoptosis rate(P=0.000)and expression of Par-4(P=0.000)and NF-κB(P=0.000),but significantly reduced insulin secretion(P=0.000).Compared with the D group,the DP group and GD group had significantly decreased apoptosis rate(P=0.000,P=0.000)and expression of Par-4(P=0.000,P=0.000)and NF-κB(P=0.000,P=0.002),but significantly improved insulin secretion(P=0.000,P=0.026).Compared with the GD group,the GDP group had significantly decreased apoptosis rate(P=0.000)and expression of Par-4(P=0.000)and NF-κB(P=0.015),but significantly improved insulin secretion(P=0.026).There were no significant differences between the DP group and the GDP group in the apoptosis rate of isletβcells(P=0.930),the expression of Par-4(P=0.965)and NF-κB(P=0.875),and insulin secretion(P=0.797).Conclusion:GLP-1 improves the apoptosis of isletβcells and insulin secretion in type 2 diabetes by inhibiting the expression of Par-4/NF-κB.
作者
雷小添
郑焱玲
甘霞光
冷蔚玲
张玲
陈兵
吴绮楠
Lei Xiaotian;Zheng Yanling;Gan Xiaguang;Leng Weiling;Zhang Ling;Chen Bing;Wu Qinan(Endocrine Department,the First Affiliated Hospital of the Army Medical University;Outpatient Department,the First Affiliated Hospital of the Army Medical University)
出处
《重庆医科大学学报》
CAS
CSCD
北大核心
2020年第3期319-323,共5页
Journal of Chongqing Medical University
基金
国家自然科学基金资助项目(编号:81370885)
西南医院军事医学科技创新计划资助项目(编号:SWH2017YBXM-12)
中华国际医学交流基金会青年医生糖尿病研究资助项目(编号:2015-N-08)。