TLR4促进苯肾上腺素诱导的心肌细胞肥大  

TLR4 promotes phenylephrine-induced cardiomyocyte hypertrophy

作　　者：韦玲[1] 闻明[1] WEI Ling;WEN Ming(Tianjin Teda Hospital,Tianjin 300457,China)

机构地区：[1]天津市泰达医院,天津300457

出　　处：《中国免疫学杂志》2020年第21期2582-2586,共5页Chinese Journal of Immunology

摘　　要：目的:探究Toll样受体4(TLR4)基因对苯肾上腺素(PE)诱导的心肌细胞肥大的影响及其作用机制。方法:选择GEO数据库中人及小鼠心肌肥厚组织的测序数据,借助R软件进行分析,筛选出目的基因TLR4;使用PE处理原代心肌细胞,检测细胞中TLR4蛋白和mRNA水平;使用siRNA转染或者腺病毒感染的方式敲低或者过表达原代心肌细胞中TLR4蛋白和mRNA水平,检测其对PE诱导的心肌细胞肥大的影响;Western blot检测敲低或者过表达TLR4对IL-6/Stat3信号通路的影响。结果:共有32个基因在人和小鼠心肌肥厚组织中表达水平发生改变;PE处理原代心肌细胞后,TLR4蛋白和mRNA水平均显著升高;敲低TLR4能抑制PE诱导的心肌细胞肥大,而上调TLR4能促进PE诱导的心肌细胞肥大;Western blot结果表明,在PE处理下,敲低TLR4能引起心肌细胞中IL-6和p-Stat3表达水平降低,过表达TLR4能导致心肌细胞中IL-6和p-Stat3表达水平显著升高。结论:TLR4在心肌肥厚过程中高表达,敲低TLR4可能通过抑制IL-6/Stat3信号通路活性抑制PE诱导的心肌细胞肥大。Objective:To explore the effect of Toll-like receptor 4(TLR4)gene on phenylephrine(PE)-induced cardiomyocyte hypertrophy and its mechanism.Methods:The sequencing data of human and mouse cardiomyocyte hypertrophy tissues in the GEO database were selected and analyzed using R software,and the target gene TLR4 was screen out.Primary cardiomyocytes were treated with phenylephrine(PE)and TLR4 protein and mRNA were detected in the cells.The TLR4 protein and mRNA levels were downregulated or overexpressed through siRNA transfection or adenovirus infection to detect the effect TLR4 in PE-induced cardiomyocyte hypertrophy.Western blot was used to detect the effect of TLR4 knockdown or overexpression on IL-6/Stat3 signal pathway.Results:A total of 32 gene expression levels were changed in both human and mouse cardiomyocyte hypertrophic tissues.TLR4 protein and mRNA levels were significantly increased after PE treatment.Knock-down the expression level of TLR4 could inhibit PE-induced cardiomyocyte hypertrophy.On the contrary,overexpression TLR4 could promote PE-induced cardiomyocyte hypertrophy.Western blot results showed that under PE treatment,knocking down TLR4 could significantly inhibit the expression levels of IL-6 and p-Stat3 in cardiomyocytes,and overexpression of TLR4 could increase the expression levels of IL-6 and p-Stat3.Conclusion:TLR4 was highly expressed in cardiomyocyte hypertrophy.Knockdown of TLR4 might inhibit PE-induced cardiomyocyte hypertrophy by inhibiting the activity of IL-6/Stat3 signaling pathway.

关 键 词：TLR4 GEO数据库 心肌肥厚 IL-6/Stat3信号通路 

分 类 号：R541[医药卫生—心血管疾病]