右美托咪定对脓毒症小鼠炎症反应的影响及机制研究

发布时间：2018-01-26 12:00

本文关键词： 脓毒症右美托咪定 miR-a 炎症反应小鼠 Toll样受体/核因子κB　出处：《中国药房》2017年19期 　论文类型：期刊论文

【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(P0.01)。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(P0.05或P0.01),但IRAK1、TRAF6 m RNA表达变化不明显(P0.05)。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(P0.05或P0.01),但IRAK1、TRAF6 m RNA表达变化不明显(P0.05)。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。
[Abstract]:Objective: to study the effect and mechanism of dexmetomidine Dexon on inflammatory response in septic mice. Methods: mice were randomly divided into normal control group and model group. Small RNA-146a(mi R-146a) inhibitor (50 mg / kg) Dex(50 渭 g / kg) and low, medium and high dose Dex groups were 100.30 mg 路kg ~ (-1) 路kg ~ (-1) 路渭 g 路kg ~ (-1). 10 rats in each group (50 渭 g 路kg ~ (-1) 路kg ~ (-1)). In addition to the normal control group, the other mice in each group were treated with IP for 6 h after IP lipopolysaccharide (IP) was used to establish septic model 0.5 h later. The expression of mi R-146a and its target gene interleukin-1 (IL-1) receptor associated kinase (IRAK1) in peripheral blood monocytes of mice in each group were detected by real-time fluorescence quantitative polymerase chain reaction (RQPCR). RNA expression of tumor necrosis factor TNFreceptor related factor 6 RNA in peripheral blood mononuclear cells (PBMC) was detected by Western blot. The expression of TRAF6 protein was detected by enzyme-linked immunosorbent assay (Elisa). Results: compared with the normal control group, the expression of miR-146a in the model group was higher than that in the control group. The level of TNF- 伪 and IL-6 was increased in IRAK1 / TRAF6 m RNA and protein expression, compared with that in the model group (P 0.01). The expression of miR-146a in peripheral blood mononuclear cells of mice in high dose group was increased, and the level of TNF- 伪 and IL-6 decreased with IRAK1. The expression of TRAF6 protein decreased by P0.05 or P0.01, but the expression of TRAF6 m RNA in IRAK1 was not significantly changed compared with the high dose group of Dex. The expression of miR-146a in peripheral blood monocytes of Dex group decreased and the level of TNF- 伪 IL-6 increased. The expression of TRAF6 protein was enhanced by P0.05 or P0.01P, but the expression of IRAK1 was increased. There was no significant change in the expression of TRAF6 m RNA. Conclusion the expression of miR-146a may be inhibited by the expression of TRAF6 m RNA in septic mice. Inhibition of the expression of two important junction proteins IRAKI and TRAF6 in the Toll like receptor 4 / NF- 魏 B pathway is related to the inhibition of the expression of IRAKI and TRAF6.
【作者单位】：泸州市人民医院麻醉科;
【分类号】：R614
【正文快照】： *主治医师。研究方向:临床麻醉。电话:0830-2361931。E-mail:guomaolzyxy@163.com改善记忆的影响及在益智食品方面的应用研究进展[J].中国供销商情:乳业导刊,2003(1):18-20.[8]王涛.普利醇抗帕金森病的药效学及其机制研究[D].北京:北京协和医学院,2009.[9]杨梅.抗帕Ⅰ号方剂治

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