摘要
目的:旨在阐明宫内发育迟缓(intrauterine growth retardation,IUGR)新生大鼠胰岛功能、内质网应激(endoplasmic reticulumstress,ERS)的改变及WFS1的表达变化,进一步探讨2型糖尿病(typ 2 diabetes mellitus,T2DM)发病相关的分子基础,为有效阻止IUGR导致T2DM提供新的治疗靶点。方法:IUGR造模组孕鼠自妊娠14 d起给予50%对照组饲料直至新生鼠出生。采用免疫组化、RT-PCR、透射电镜和Western blot技术观察新生鼠胰腺中WFS1和ERS变化情况。结果:①IUGR大鼠胰腺及成年大鼠胰岛中WFS1、GRP78的表达明显增加(P<0.05,n=10)。②电镜下IUGR新生鼠胰腺中内质网明显肿胀、融合。③胰腺葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78/Bip)和C/EBP同源蛋白(CHOP)在IUGR新生大鼠胰腺和成年大鼠胰岛中表达明显升高。结论:WFS1可能通过ERS参与IUGR导致的胰岛功能损伤。
Objective:The aim of this study is to clarify ERS and the expression level of WFS1 in IUGR newborn rats,further exploring the molecular basis related to T2 DM,which may provide a new therapy for preventing IUGR from leading to T2 DM.Methods:The pregnant rats in the IUGR group were fed 50%calorie restriction from gestational day 14 until term.Immunohistochemistry,RT-PCR,transmission electron microscope and western blot were applied.Results:①The expressions of WFS1 and GRP78 in the pancreas and islets of IUGR rats were increased(P<0.05,n=10).②Electron microscope showed that the endoplasmic reticulums in the pancreas of newborn IUGR rats were swollen and fused.③Glucose-regulated protein 78(GRP78/Bip)and CHOP were significantly elevated in the pancreas and islets of IUGR.Conclusion:This study demonstrated that WFS1 might play roles in maintaining islet structure and function in IUGR rats,maybe partly via UPR.
作者
戴程婷
袁逸
李一卉
袁庆新
DAI Chengting;YUAN Yi;LI Yihui;YUAN Qingxin(Department of Endocrinology,the First Affiliated Hospital of Nanjing Medical Unversity,Nanjing 210029,China)
出处
《南京医科大学学报（自然科学版）》
CAS
CSCD
北大核心
2020年第5期658-662,共5页
Journal of Nanjing Medical University(Natural Sciences)
基金
国家自然科学基金(81570697,81170715)。
关键词
WFS1
宫内发育迟缓
胰岛功能
糖尿病
内质网应激
WFS1
intrauterine growth retardation
islet function
type 2 diabetes mellitus
endoplasmic reticulum stress
