右美托咪定通过Toll样受体4减轻小鼠肺缺血/再灌注损伤  

Dexmedetomidine decreases TLR4 expression to alleviate lung ischemia/reperfusion injury in mice

作　　者：梁磊 邓林[1] 谢冕[1] 郭波[1] LIANG Lei;DENG Lin;XIE Mian;GUO Bo(Dept.of Anesthesiology,Chongqing Traditional Chinese Medicine Hospital,Chongqing 400020,China)

机构地区：[1]重庆市中医院麻醉科,重庆400020

出　　处：《基础医学与临床》2018年第7期967-972,共6页Basic and Clinical Medicine

基　　金：重庆市卫生计生委中医药科技项目(zy201602172)

摘　　要：目的探讨盐酸右美托咪定(Dex)对小鼠肺缺血/再灌注损伤(LIRI)的保护作用机制。方法将野生型(WT)和Toll样受体4敲除(TLR4-/-)C57BL/6雌鼠,随机分为:假手术组(S组)、LIRI组(I/R组)、0.9%Na Cl组(NS组)和Dex干预组(D组)。肺组织HE染色;RT-q PCR检测肺组织TLR4 mRNA的表达;ELISA检测肺组织中TNF-ɑ、IL-6和IL-1β(WT和TLR4-/-)水平;Western blot检测肺组织Nod样受体蛋白3(NLRP3)炎性小体表达量。结果 Dex明显改善WT小鼠肺缺血/再灌注病理损伤,显著降低其肺组织中TLR4表达和多种前炎性因子的产生(P<0.01),抑制NLRP3炎性小体的产生和活化(P<0.01)。但是在TLR4-/-小鼠中未观察到对各种炎性因子的抑制作用。结论 Dex可通过抑制TLR4的表达,减少前炎性因子释放和NLRP3炎性小体的形成与活化,达到保护LIRI的作用。Objective To investigate the protective mechanism of dexmedetomidine(Dex)hydrochloride to lung ischemia/reperfusion injury(LIRI)in mice.Methods The wild type(WT)and Toll-like receptor 4 knockout(TLR 4-/-)C57BL/6 Balb/c female mouse randomly divided into four groups:sham group(S group),pulmonary ischemia/reperfusion group(I/R group),normal saline group(NS group)and Dex group(D group).In S group,the chest was opened only,but in I/R group,NS group and D group,model of lung ischemia/reperfusion injury in mice was made by clamping left pulmonary hilum for 30 min,and then reperfusion for 3 h.The lung tissue was observed by HE staining.RT-qPCR detected the expression of TLR4 mRNA,and ELISA measured the TNF-α,IL-6 and IL-1 levels,including WT and TLR4-/-.Western blot measured the expression of NLRP3 in lung tissue in both WT and TLR 4-/-.Results Dex significantly decreased the pathological damage of LIRI,reduced the expression of levels of TLR4 mRNA and the production of inflammatory cytokines(P<0.01),and also suppress production and activation of NLRP3(P<0.01)in lung ischemia/reperfusion tissue in WT mice.But no cytokines was found to be inhibited in TLR 4-/-mice.Conclusions Dex may decrease the release of a variety of pro-inflammatory factors and inhibit production and activation of NLRP3 inflammasome by TLR4,thereby protect lung against LIRI.

关 键 词：右美托咪定 肺缺血/再灌注 TLR4 炎性因子 

分 类 号：R614[医药卫生—麻醉学]