中华糖尿病杂志2024,Vol.16Issue(5) :527-534.DOI:10.3760/cma.j.cn115791-20240221-00077

胰腺和脑β淀粉样蛋白表达在小鼠2型糖尿病进程中同步变化的研究

Synchronization of β-amyloid protein expression in pancreas and brain during progression of type 2 diabetes mellitus in mice

谢磊 徐嘉璐 范荣萍 陶静 杨雁
中华糖尿病杂志2024,Vol.16Issue(5) :527-534.DOI:10.3760/cma.j.cn115791-20240221-00077

胰腺和脑β淀粉样蛋白表达在小鼠2型糖尿病进程中同步变化的研究

Synchronization of β-amyloid protein expression in pancreas and brain during progression of type 2 diabetes mellitus in mice

谢磊 1徐嘉璐 1范荣萍 1陶静 1杨雁1
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作者信息

  • 1. 华中科技大学同济医学院附属同济医院内分泌科,武汉 430030
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摘要

目的 观察2型糖尿病(T2DM)小鼠胰腺和大脑组织β淀粉样蛋白(Aβ)随T2DM病程进展的表达情况.方法 36只对照组小鼠及36只T2DM小鼠通过简单随机化分组各分为6组:13周龄组、16周龄组、19周龄组、22周龄组、25周龄组、28周龄组.从13周龄开始,每隔3周处死一组小鼠,总共观察时间为13~28周.采用免疫组织化学染色法和酶联免疫吸附测定(ELISA)法观察T2DM小鼠Aβ在胰腺和大脑组织的分布及表达情况;通过Western blotting和ELISA法观察淀粉样前体蛋白(APP)以及β位点APP裂解酶-1(BACE-1)的表达情况.两组间比较采用t检验,多组间比较采用单因素方差分析.采用Spearman相关性分析法分析胰腺Aβ含量与稳态模型评估胰岛素抵抗指数(HOMA-IR)和胰岛素/胰岛素原比值之间的相关性.结果 随着T2DM小鼠病程的进展,与对照组小鼠相比,T2DM小鼠胰腺胰岛及大脑海马区Aβ沉积逐渐加重(P<0.05).T2DM小鼠胰腺和大脑海马组织中Aβ的含量随病程进展呈一致的逐渐升高的趋势(P<0.05).两种组织中APP和BACE-1的表达水平随病程进展呈一致的先升高后下降的趋势(P<0.05).Spearman相关性分析结果显示,随着病程进展,T2DM组小鼠的胰岛功能水平逐渐下降,并且与逐渐增加的胰腺Aβ沉积具有相关性,其中,HOMA-IR和胰岛素/胰岛素原与胰腺Aβ沉积的相关系数分别为0.837 0和0.728 1(P<0.001).结论 T2DM小鼠胰腺和大脑组织Aβ随病程进展的表达水平存在同步变化的现象.

Abstract

Objective To observe the expression of β-amyloid(Aβ)in pancreas and brain of type 2 diabetes mellitus(T2DM)mice during the progression of T2DM.Methods A total of 36 control mice and 36 T2DM mice were randomly divided into 6 groups(13 weeks,16 weeks,19 weeks,22 weeks,25 weeks,28 weeks).One group of mice was sacrificed at 3-week intervals starting at 13 weeks of age,and the total observation period was from 13 weeks to 28 weeks.Immunohistochemical analysis and enzyme-linked immunosorbent assay(ELISA)were used to observe the distribution and expression of Aβ in pancreas and brain tissue of T2DM mice.Western blotting and ELISA were used to detect the expression of amyloid precursor protein(APP)and β-site amyloid precursor protein cleavage-1(BACE-1).The t-test was used for comparison between two groups,and one-way analysis of variance was used for comparison between multiple groups.Spearman correlation analysis was used to analyze the correlation between pancreatic Aβ content and homeostasis model assessment of insulin resistance index(HOMA-IR)and insulin/proinsulin ratio.Results With the progression of T2DM,the deposition of Aβ in pancreatic islets and brain hippocampus gradually worsened compared with control mice(P<0.05).The expression of Aβ in pancreas and hippocampus of T2DM mice were gradually increased with the progress of T2DM(P<0.05).The expression levels of APP and BACE-1 in the two tissues initially increased and then decreased with disease progression(P<0.05).In addition,with the progression of the disease,the level of pancreatic islet function in the T2DM group gradually decreased,which was significantly correlated with the gradual increase of pancreatic Aβ deposition.Spearman correlation analysis showed that the correlation coefficients of HOMA-IR and insulin/proinsulin with pancreatic Aβdeposition were 0.837 0 and 0.728 1,respectively(P<0.001).Conclusion The expression of Aβ in the pancreas and brain of T2DM mice changes in synchrony with disease progression.

关键词

糖尿病,2型/阿尔茨海默病/β淀粉样蛋白/同步化

Key words

Diabetes mellitus,type 2/Alzheimer's disease/Amyloid-beta protein/Synchronization

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基金项目

国家自然科学基金(81974114)

出版年

2024
中华糖尿病杂志
中华医学会

中华糖尿病杂志

CSTPCDCSCD北大核心
影响因子:1.65
ISSN:1674-5809
参考文献量1
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