肥胖大鼠海马内TNF-α、胰岛素降解酶、PPARγ和Aβ的表达及其作用  

Expression of TNF-α,IDE,PPAR γ and Aβ in hippocampus of obese rats

作　　者：杨思思[1] 姜腾[1] 张木勋[1] 

机构地区：[1]华中科技大学附属同济医院内分泌科,湖北武汉430030

出　　处：《中国病理生理杂志》2012年第10期1756-1760,共5页Chinese Journal of Pathophysiology

摘　　要：目的:检测肥胖大鼠海马内肿瘤坏死因子α(tumor necrosis factorα,TNF-α)、胰岛素降解酶(in-sulin-degrading enzyme,IDE)、过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)和淀粉样β肽(amyloidβ-peptide,Aβ)水平,探讨TNF-α对肥胖大鼠海马内IDE和Aβ的影响,观察TNF-α、Aβ与PPARγ的关系。方法:建立肥胖(obesity,OB)大鼠模型;葡萄糖氧化酶法检测大鼠血糖水平,放射免疫法测血浆胰岛素水平;实时荧光定量PCR检测大鼠海马内TNF-α、淀粉样β蛋白前体(amyloidβ-protein precur-sor,APP)、PPARγ及IDE的mRNA水平;蛋白免疫印记技术及免疫组织化学染色法检测大鼠海马内TNF-α、Aβ42(由APP降解产生)、PPARγ及IDE的蛋白表达。结果:OB组大鼠血糖较正常组无明显差别,胰岛素明显升高并存在胰岛素抵抗(P<0.05);实时荧光定量PCR结果显示肥胖大鼠海马内TNF-α和APP mRNA水平较正常组升高(P<0.01),而PPARγ和IDE mRNA表达减少(P<0.01);蛋白免疫印记技术及免疫组织化学法检测与实时荧光定量PCR结果一致。结论:肥胖时大鼠海马内存在炎性改变,TNF-α表达升高,IDE和PPARγ表达减少,Aβ沉积增加。IDE作为Aβ的重要降解酶,其表达减少是Aβ沉积的关键因素;PPARγ作为调控IDE转录的核转录因子,在本实验肥胖大鼠海马内表达下降,提示IDE生成减少可能与PPARγ作用下降有关。AIM ： To observe the expression of TNF - α, insulin - degrading enzyme （ IDE）, peroxisome proliferator- activated receptor T （PPART） and amyloid β- peptide（Aβ） in hippocampus of obese rats. METHODS： The SD rats were fed with high glucose, high fat and high protein for 12 weeks to establish the model of obesity （OB）. The plasma insulin level was measured by radioimmunoassay, and the plasma glucose was detected by glucose oxidase method. The indexes of insulin resistance were calculated by HOMA - IR. The expression of TNF -α, PPART, IDE and amyloid β- protein precursor （APP） mRNA in hippocampus were analyzed by real- time fluorescence quantitative PCR, and the protein levels of TNF -α, Aβ42, PPARγand IDE were determined by the methods of Western blotting and immunochemis- try. RESULTS ： The plasma insulin and insulin resistance calculated by HOMA - IR were significantly higher in OB group than those in control group. The mRNA level of TNF - α and APP were up - regulated in OB group, while the levels of PPARγ and IDE were decreased. The results of Western blotting and immunochemistry were the same as those of real - time fluorescence quantitative PCR. CONCLUSION： In the hippocampus of obese rats, inflammatory changes exist. The increase in Aβ in obese rats may be due to the down - regulation of IDE, a degrading enzyme of Aβ, and the decrease in PPARγexpression, which regulates the transcription of IDE.

关 键 词：肥胖症 胰岛素降解酶 淀粉样β肽类 肿瘤坏死因子 过氧化物酶体增殖物激活受体Γ 

分 类 号：R363[医药卫生—病理学]