硫氧还蛋白相互作用蛋白降低GLP-1促小鼠胰岛β细胞的增殖效应  

TXNIP reduces pro-proliferation effect of GLP-1 on mouse isletβcells

作　　者：张文婷 王瑾[1] 岳继萍 靳文文 张志楠 焦向英[1] ZHANG Wen-ting;WANG Jin;YUE Ji-ping;JIN Wen-wen;ZHANG Zhi-nan;JIAO Xiang-ying(Department of Physiology, Shanxi Medical University, Taiyuan 030001, China)

机构地区：[1]山西医科大学生理学系,山西太原030001

出　　处：《基础医学与临床》2020年第8期1076-1082,共7页Basic and Clinical Medicine

基　　金：山西省面上青年基金(201801D221401)。

摘　　要：目的观察硫氧还蛋白相互作用蛋白(TXNIP)在胰高血糖素样肽-1(GLP-1)促小鼠胰岛β细胞的增殖效应中的作用。方法小鼠分为db/m组和db/db组,每组10只;慢病毒构建TXNIP过表达(Ad-TXNIP-GFP)稳转小鼠胰岛β细胞株MIN6细胞,分为对照组、Ad-GFP组和Ad-TXNIP-GFP组。Western blot检测TXNIP、增殖细胞核抗原(PCNA)和GLP-1受体(GLP-1R)的表达,HE和免疫荧光观察胰岛形态和β细胞数量,GLP-1R、Ki67,ELISA检测小鼠血清中GLP-1的表达,免疫组化检测GLP-1R水平。结果db/db鼠胰岛形态破坏且β细胞数量减少;胰腺组织PCNA表达降低(P<0.05);血清GLP-1水平降低(P<0.05);胰腺组织和胰岛GLP-1R水平降低(P<0.05);胰腺组织TXNIP表达升高(P<0.05);TXNIP过表达细胞模型构建成功(P<0.05);TXNIP过表达时GLP-1R水平降低(P<0.05);TXNIP过表达使GLP-1对胰岛β细胞的增殖效应降低(P<0.05)。结论TXNIP作用于GLP-1R从而降低GLP-1对小鼠胰岛β细胞的增殖效应。Objective To observe the role of thioredoxin interacting protein(TXNIP)in the proliferation of isletβcells promoted by Glucagon-like peptide 1(GLP-1).Methods The mice were divided into db/m group and db/db group;TXNIP over-expression(Ad-TXNIP-GFP)MIN6 cells were constructed by stably transfected with lentivirus,which were divided into control group,Ad-GFP group and Ad-TXNIP-GFP group.Western blot was used to detect the expression of TXNIP and proliferating cell nuclear antigen(PCNA)in pancreatic tissues of db/m and db/db mice.The morphology of the islets,the number ofβcells,GLP-1R and Ki67 were observed by HE and immunohistochemistry method.The expression of GLP-1 in serum was detected by ELISA.The level of GLP-1R protein in pancreatic tissue was detected by immunohistochemistry.Results Islet structure was destructed,the number ofβcells and PCNA expression decreased in pancreatic tissue of db/db mice(P<0.05).The level of GLP-1 in serum reduced(P<0.05),and the level of GLP-1 receptor in pancreatic tissue and islet was reduced(P<0.05).The expression of TXNIP in pancreatic tissues of db/db mice increased(P<0.05).The TXNIP overexpression cell model was successfully constructed(P<0.05),and the level of GLP-1 receptordecreased in isletβcells(P<0.05).The overexpression of TXNIP reduced the proliferative effect of isletβcells to GLP-1(P<0.05).Conclusions TXNIP acts on the GLP-1 receptor to reduce the proliferation of isletβcells promoted by GLP-1.

关 键 词：硫氧还蛋白相互作用蛋白 GLP-1 GLP-1受体 细胞增殖 

分 类 号：R335.6[医药卫生—人体生理学] R587.1[医药卫生—基础医学]