艾塞那肽4对严重烫伤大鼠胰岛Wnt/β-catenin信号通路的调控机制  

The regulatory mechanism of exenatide 4 on the Wnt/β-catenin signaling pathway in islets of severely scal-ded rats

作　　者：孙鹏超 张博涵 申传安[2] 李大伟[2] 钮跃增 SUN Peng-chao;ZHANG Bo-han;SHEN Chuan-an;LI Da-wei;NIU Yue-zeng(Graduate Base of Jinzhou Medical University at The Fourth Medical Center of Chinese PLA General Hospital,Bei-jing 100048,China;Department of Burns and Plastic Surgery,The Fourth Medical Center of Chinese PLA Gener-al Hospital,Beijing 100048,China)

机构地区：[1]锦州医科大学解放军总医院第四医学中心研究生培养基地,北京100048 [2]解放军总医院第四医学中心烧伤整形科,北京100048

出　　处：《医学研究生学报》2020年第12期1250-1255,共6页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81373140)。

摘　　要：目的严重烫伤后机体会出现糖代谢紊乱,给予GLP-1类似物艾塞那肽4治疗会使糖代谢紊乱得到改善,且Wnt/β-catenin信号通路与胰腺的发育以及胰岛素的分泌密切相关。文章探讨艾塞那肽4对严重烫伤大鼠胰岛Wnt/β-catenin信号通路的调节机制。方法将Wistar大鼠随机分为假烫组、烫伤组、假烫+艾塞那肽4组以及烫伤+艾塞那肽4组,每组12只。烫伤组及烫伤+艾塞那肽4组大鼠用94℃热水浸浴背部12 s、腹部6 s,制造50%TBSA Ⅲ°烫伤;假烫组及假烫+艾塞那肽4组大鼠在37℃温水中浸浴相同部位和时间模拟致伤;烫伤+艾塞那肽4组及假烫+艾塞那肽4组在致伤后腹腔注射艾塞那肽4 4μg/kg,2次/d,烫伤组和假烫组大鼠腹腔注射等量灭菌注射用水,2次/d。伤后72 h检测空腹血糖、血清胰岛素以及腹腔糖耐量水平,分离胰岛,采用Westen blot法检测胰岛中β-Catenin蛋白以及TCF7L2蛋白表达水平,采用RT-qPCR法检测大鼠胰岛中Preproinsulin以及TCF7L2 mRNA转录水平。结果与假烫组空腹血糖[(4.7±0.4)mmol/L]相比,烫伤组[(7.0±0.7) mmol/L]及烫伤+艾塞那肽4组[(5.6±0.5) mmol/L]明显升高(P<0.01);与烫伤组相比,烫伤+艾塞那肽4组空腹血糖浓度明显降低(P<0.01)。与假烫组相比,烫伤组及烫伤+艾塞那肽4组血清胰岛素浓度明显升高(P<0.01),糖耐量水平AUC值亦明显降低(P<0.01),β-Catenin及TCF7L2蛋白表达水平明显降低(P<0.01),Preproinsulin及TCF7L2 mRNA转录明显降低(P<0.01)。与烫伤组相比,烫伤+艾塞那肽4组血清胰岛素浓度明显升高(P<0.01),糖耐量水平升高(P<0.01),β-Catenin及TCF7L2蛋白表达水平明显升高(P<0.01),Preproinsulin及TCF7L2 mRNA转录明显升高(P<0.01)。结论严重烫伤早期大鼠胰岛Wnt/β-catenin信号通路活性下降,艾塞那肽4可能通过提高大鼠胰岛中Wnt/β-catenin信号通路活性增加TCF7L2表达,从而提高胰岛素转录及表达并改善烫伤后机体的糖代谢状态。Objective The glucose metabolism disorder after severe scald can be ameliorated by the treatment with Exendin-4,a GLP-1 analogue.The Wnt/β-catenin signaling pathway is closely related to pancreatic development and insulin secretion.Hence,the purpose of this study was to explore the effects and mechanism of Exendin-4 on regulating the Wnt/β-catenin signaling pathway in pan-creatic islets of severely scalded rats.Methods Wistar rats were randomly divided into a sham group(C),scald group(S),sham+Exendin-4 group(CE),and scald+Exendin-4 group(SE)accord-ing to the random number table,12 per group.Rats in groups S and SE were immersed in hot water at 94℃ for 12 seconds on their back and 6 seconds on the abdomen,causing full-thickness scald injuries involving 50%total body surface area(TBSA),while rats in groups C and CE were immersed in 37℃warm water for the paralIel ex-periments to simulate injuries at the same locations.After injury creation,rats in groups CE and SE were injected intraperitoneally with Exendin-4(4μg/kg),while rats in groups S and Cwere injected intraperitoneally with sterilized water for injection twice per day.Fasting blood glucose(FBG)levels were measured 72 h postinjury;serum insulin levels and intraperitoneal glucose tolerance were de-tected;the expression of nonphospho(active)β-catenin and TCF7L2 were detected by western blot after isolating the islets;the tran-scription levels of preproinsulin and TCF7L2 mRNAs in the pancreatic islets were examined by realtime fluorescent quantitative polymerase chain reaction(RT-qPCR).Results The FBG levels,area under the curve(AUC)and serum insuln levels increased sig-nificantly,while the expression of non-phospho(active) β-catenin and TCF7L2,as well as the transcription of preproinsulin and TCF7L2,decreased in group S.Compared with group S,the FBG levels,AUC and serum insulin levels decreased significantly,while the expression of non phospho(active)β-catenin and TCF7L2,as well as the transcription of preproinsulin and TCF7L2,increased in groups SE.C

关 键 词：烫伤 WNT/Β-CATENIN信号通路 胰岛素 胰岛 

分 类 号：R285.5[医药卫生—中药学]