右美托咪定对脓毒症小鼠炎症反应的影响及机制研究  

Study on the Effect and Its Mechanism of Dexmedetomidine on the Inflammatory Response in Septic Mice

作　　者：郭茂[1] 王文明[1] 

机构地区：[1]泸州市人民医院麻醉科,四川泸州646000

出　　处：《中国药房》2017年第19期2651-2654,共4页China Pharmacy

摘　　要：目的:研究右美托咪定(Dex)对脓毒症小鼠炎症反应的影响及机制。方法:将小鼠随机分为正常对照组、模型组、微小RNA-146a(mi R-146a)抑制剂(50 mg/kg)+Dex(50μg/kg)组和Dex低、中、高剂量组(10、30、50μg/kg),每组10只。除正常对照组外,其余各组小鼠ip脂多糖建立脓毒症模型,0.5 h后ip相应药物。药物干预6 h后,实时荧光定量聚合酶链式反应法检测各组小鼠外周血单核细胞中mi R-146a表达及其靶基因白细胞介素1(IL-1)受体相关激酶(IRAK1)、肿瘤坏死因子(TNF)受体相关因子6(TRAF6)m RNA表达,Western blot法检测外周血单核细胞中IRAK1、TRAF6蛋白的表达,酶联免疫吸附法检测血清中TNF-α、IL-6的水平。结果:与正常对照组比较,模型组小鼠的mi R-146a表达增强,TNF-α、IL-6水平升高,IRAK1、TRAF6 m RNA和蛋白表达增强(P<0.01)。与模型组比较,Dex中、高剂量组小鼠外周血单核细胞中mi R-146a表达增强,TNF-α、IL-6水平下降,IRAK1、TRAF6蛋白表达减弱(P<0.05或P<0.01),但IRAK1、TRAF6 m RNA表达变化不明显(P>0.05)。与Dex高剂量组比较,mi R-146a抑制剂+Dex组小鼠外周血单核细胞中mi R-146a表达减弱,TNF-α、IL-6水平升高,IRAK1、TRAF6蛋白表达增强(P<0.05或P<0.01),但IRAK1、TRAF6 m RNA表达变化不明显(P>0.05)。结论:Dex可抑制脓毒症小鼠炎症反应,其机制可能与诱导mi R-146a表达、抑制Toll样受体4/核因子κB通路中的两个重要接头蛋白IRAKI和TRAF6的表达有关。OBJECTIVE：To study the effect and its mechanism of dexmedetomidine（Dex）on inflammatory response in septic mice. METHODS：Mice were randomly divided into normal control group,model group,mi R-146 a inhibitor（50 mg/kg）＋ Dex（50 μg/kg）group,Dex low-dose,medium-dose,high-dose groups（10,30,50 μg/kg）,10 in each group. Except for normal control group,other groups were intraperitoneally injected lipopolysaccharide to induce septic models,intraperitoneally injected relevant medicines after 0.5 h. After drug intervention for 6 h,mi R-146 a expression,IRAK1 and TRAF6 m RNA expressions in peripheral blood mononuclear cells in each group were detected by real-time fluorescence quantitative polymerase chain reaction method.IRAK1,TRAF6 protein expressions in peripheral blood mononuclear cells in each group were detected by Western blot method.TNF-α,IL-6 levels in serum were detected by enzyme-linked immunosorbent method. RESULTS：Compared with normal control group,mi R-146 a expression,TNF-α and IL-6 levels,IRAK1,TRAF6 m RNA and protein expressions in peripheral blood mononuclear cells in model group were increased（P〈0.01）. Compared with model group,mi R-146 a expression in peripheral blood mono-nuclear cells in Dex medium-dose,high-dose groups were increased;TNF-α and IL-6 levels,IRAK1,TRAF6 protein expressions were decreased（P〈0.05 or P〈0.01）;while IRAK1,TRAF6 m RNA expressions changed less obviously（P〉0.05）. Compared with Dex high-dose group,mi R-146 a expression,in peripheral blood mononuclear cells in mi R-146 a inhibitor＋Dex group was decreased;TNF-α and IL-6 levels,IRAK1,TRAF6 protein expressions were increased（P〈0.05 or P〈0.01）;while IRAK1,TRAF6 m RNA expressions changed less obviously（P〉0.05）. CONCLUSIONS：Dex can inhibit the inflammatory response in septic mice. The mechanism may associate with inducing mi R-146 a expression and inhibiting the 2 important adaptor proteins IRAK1,TRAF6 expressions in Toll-like receptor 4/nuclear factor-κB pathway.

关 键 词：脓毒症 右美托咪定 MIR-146A 炎症反应 小鼠 Toll样受体4/核因子κB 

分 类 号：R971.2[医药卫生—药品]