摘要
目的:观察依托咪酯对内毒素急性肺损伤小鼠炎症反应的影响,并探讨其作用机制。方法:雄性成年BLAB/c小鼠60只,随机分为空白对照组、模型组、依托咪酯组,每组20只。模型组及药物干预组应用腹腔注射脂多糖(LPS,20 mg/kg)制作急性肺损伤小鼠模型,空白对照组给予等体积生理盐水腹腔注射。药物干预组于造模后0.5 h给予依托咪酯2.5 mg/kg。空白对照组及模型组给予等体积生理200μl/只。于给药后6 h检测小鼠血清中的内毒素水平,BALF中TNF-α、IL-6和IL-1β的含量;RT-PCR检测miR-146a、MyD88、IRAK1、IRF5、TRAF6 mRNA在肺组织中的表达;Western blot检测TLR4、MyD88、TRAF6、IRAK1、IRF5蛋白在肺组织中的表达。结果:模型组、依托咪酯组与空白对照组相比,血清内毒素含量、TNF-α、IL-6和IL-1β含量、miR-146a表达水平、TLR4、MyD88、IRAK1、IRF5、TRAF6 mRNA表达水平及TLR4、MyD88、IRAK1、IRF5、TRAF6蛋白表达均明显升高,差异具有统计学意义(P<0.05);依托咪酯组与模型组比较,小鼠血清内毒素含量、TNF-α、IL-6和IL-1β含量、TLR4、MyD88、IRAK1、IRF5、TRAF6 mRNA表达水平及TLR4、MyD88、IRAK1、IRF5、TRAF6蛋白表达水平均明显下降,差异具有统计学意义(P<0.05)。结论:依托咪酯能够通过增加miR-146a的含量调节TLR4通路对内毒素急性肺损伤小鼠炎症反应的保护作用。
Objective:To observe the effect and mechanism of etomidate on inflammatory response in mice with endotoxin-induced acute lung injury.Methods:60 male adult BLAB/c mice were randomly divided into blank control group,model group and etomidate group,with 20 rats in each group.The model group and drug intervention group were induced by intraperitoneal injection of 20 mg/kg,while the blank control group was gave intraperitoneal injection of normal saline of equal volume.The drug intervention group was gave etomidate 2.5 mg/kg 0.5 h after the establishment of the model.The blank control group and model group were gave 200 μl of isovolumic physiology.The levels of endotoxin in serum,TNF-α,IL-6 and IL-1β in BALF were detected 6 hours after administration.The expression of miR-146 a,MyD88,IRAK1,IRF5 and TRAF6 mRNA in lung tissues were detected by RT-PCR.The expression of TLR4,MyD88,TRAF6,IRAK1 and IRF5 proteins in lung tissues were detected by Western blot.Results:Compared with the blank control group,the levels of serum endotoxin,TNF-α,IL-6 and IL-1β,the expression of miRNA-146 a,TLR4,MyD88,IRAK1,IRF5,TRAF6 and the expression of TLR4,MyD88,IRAK1,IRF5 and TRAF6 were significantly increased in the model group and etomidate group,the difference was statistically significant(P<0.05).Compared with model group,the levels of serum endotoxin,TNF-α,IL-6 and IL-1β,TLR4,MyD88,IRAK1,IRF5,TRAF6 and the expression of TLR4,MyD88,IRAK1,IRF5 and TRAF6 were significantly decreased in etomidate group,the difference was statistically significant(P<0.05).Conclusion:Etomidate can modulate the protective effect of the TLR4 pathway on the inflammatory response in mice with endotoxin-induced acute lung injury by increasing the amount of miR-146 a.
作者
安静
张睿
刘晓乐
AN Jing;ZHANG Rui;LIU Xiao-Le(Department of Anesthesiology,Henan Provincial Hospital,Zhengzhou 450000,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2020年第2期159-163,共5页
Chinese Journal of Immunology
