STAT3在Aβ寡聚体诱导的小胶质细胞炎症反应中的作用

The role of STAT3 in the inflammatory response of microglia induced by beta amyloid

目的研究β-淀粉样蛋白(Aβ)诱导小胶质细胞产生炎症反应中信号转导和转录激活子3(STAT3)的表达水平及作用。方法用蛋白印迹法检测STAT3在Aβ寡聚体诱导的BV2小胶质细胞炎症反应中的表达水平;用siRNA沉默STAT3的表达后,实验分为正常对照组、siRNA STAT3组、Aβ处理组、Control siRNA+Aβ组以及siRNA STAT3+Aβ组,用实时荧光定量PCR和酶联免疫吸附法(ELISA)检测IL1-β、TNF-αmRNA和蛋白的表达水平。结果 Aβ寡聚体处理小胶质细胞后p-STAT3的表达水平增高,与Aβ寡聚体的浓度和处理时间有关。siRNA沉默STAT3使其mRNA和蛋白表达分别下降约67%和65%;与正常对照组相比,Aβ处理组的IL1-β及TNF-αmRNA和蛋白的表达水平增高;与Aβ处理组相比,siRNA STAT3+Aβ组的IL1-β及TNF-αmRNA和蛋白的表达水平降低。结论 STAT3参与调控Aβ寡聚体诱导的小胶质细胞炎症反应中炎症因子的释放,在阿尔茨海默氏病(AD)的Aβ作用机制中可能有一定的作用。

Objective To investigate the expression level and function of signal transducer and activator of tran -scription 3 （STAT3） in the inflammatory response of microglia induced by beta amyloid .Methods The expression level of STAT3 in the inflammatory responses of microglia induced by beta amyloid was detected by Western blotting ;After the STAT3 was silent by siRNA,the experimental groups were divided into normal control ,siRNA STAT3,Aβgroup,Control siRNA＋Aβ,siRNA STAT3＋Aβ,then the mRNA and protein expression levels of IL 1-βand TNF-αwere measured by real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay （ ELISA ） .Results The p-STAT3 ex-pression increased in microglia treated with Aβoligomers and was related to Aβoligomers concentration and time .STAT3 siRNA marked its mRNA and protein expression decreased about 67%and 65%respectively;compared to the normal con-trol group,the mRNA and protein expression levels of IL 1-βand TNF-αof Aβgroup increased;and compared to Aβgroup, the mRNA and protein expression levels of IL 1-βand TNF-αof siRNA STAT3 ＋Aβgroup decreased .Conclusion STAT3 was involved in the regulation of the release of inflammatory cytokines in the inflammatory response of microglia in -duced by Aβoligomers,playing a certain role in the pathogenesis of Aβof Alzheimer’s disease（AD）.