坎地沙坦对脂多糖刺激巨噬细胞炎症因子释放的影响  

Effects of candisartan on expression of inflammatory cytokines by macrophages stimulated by lipopolysaccharides

作　　者：艾文伟[1] 张明[2] 雷梦觉[1] 胡杰[1] 孟哲 高登峰[3] AI Wenwei;ZHANG Ming;LEI Mengjue;HU Jie;MENG Zhe;GAO Dengfeng(Cardiology Two Subjects,Second Department of Jiangxi Provincial People′s Hospital,Nanchang 330006,China)

机构地区：[1]江西省人民医院二部心内二科,南昌330006 [2]江西省人民医院二部心内一科,南昌330006 [3]西安交通大学第二附属医院心内科,西安710004

出　　处：《实用医学杂志》2019年第7期1044-1047,共4页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:81570382)

摘　　要：目的研究坎地沙坦对脂多糖(LPS)刺激巨噬细胞炎症因子释放的影响。方法 MTT法测定不同浓度坎地沙坦对RAW264.7细胞活性的影响。将细胞分为5组:对照组、LPS干预组、LPS+坎地沙坦10^(-7)mol/L组、LPS+坎地沙坦10^(-6)mol/L组和LPS+坎地沙坦10^(-5)mol/L组。real-time RT-PCR和Western-blot测定各组细胞Toll样受体4(TLR4)、髓样分化因子88(Myd88)和核转录因子NF-κB(p65)mRNA和蛋白的表达;ELISA测定各组细胞上清液IL-1β和TNF-α分泌水平。结果同对照组相比,坎地沙坦可以有效抑制LPS诱导的TLR4、MyD88和NF-κB(p65)的mRNA表达和致炎细胞因子的释放,并具有剂量依赖性(P <0.01)。结论坎地沙坦能够减少巨噬细胞炎症因子IL-1β和TNF-α的分泌,这一作用可能部分通过抑制TLR4-Myd88-NF-κB传导通路的活化得以实现。Objective To explore the influence of candesartan on the inflammatory cytokine expression of macrophage stimulated by Lipopolysaccharides(LPS).Methods Murine macrophage line(RAW264.7 cell)were stimulated with different concentration candesartan for 24 h,and then cell activity was observed by MTT assay.Cells were pretreated with different concentration candesartan(10^-7,10^-6 and 10^-5μmol/L)for 1 h,and then stimulated with LPS(500 ng/mL)for 4,9 or 24 h.mRNA and protein of Toll like receptor 4(TLR4),myeloid differentiation primary response gene 88(Myd88)and Nuclear factorκB(N FκB)were determined by real time PCR and Western blot;IL-1βand TNF-αconcentration were detected by ELISA.Results Candesartan effectively inhibited mRNA and protein expressions of TLR4,Myd88 and NF-κB(p65)and secretion of IL-1βand TNF-αin macrophage stimulated by LPS,with concentration dependent manners.Conclusion Candesartan has inhibitory effect on inflammtory cytokine expression with a concentration dependent manner in macrophage stimulated by LPS,and this effect was also partly associated with inactivity of TLR4-Myd88-NF-κB signaling pathway.

关 键 词：坎地沙坦 巨噬细胞 TOLL样受体-4 白细胞介素1Β 肿瘤坏死因子-Α 

分 类 号：R965[医药卫生—药理学]