宫内发育迟缓新生大鼠胰WFS1的表达变化及其可能作用
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国家自然科学基金(81570697,81170715)


The effects of WFS1 on pancreatic islet β cell function in rats born with intrauterine growth retardation
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    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。

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    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 T2DM,which may provide a new therapy for preventing IUGR from leading to T2DM. 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). ② Electron 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.

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戴程婷,袁 逸,李一卉,袁庆新.宫内发育迟缓新生大鼠胰WFS1的表达变化及其可能作用[J].南京医科大学学报(自然科学版),2020,(5):658-662

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  • 收稿日期:2019-10-09
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  • 在线发布日期: 2020-06-10
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