乌司他丁对创伤失血性休克大鼠肺炎症介质及其信号通路miR-146a调控TLR4/NF-κB的影响研究  

Research on the impacts of ulinastatin on the regulation of TLR4/NF-κB by pulmonary inflammatory mediators and the signaling pathway of miR-146a in rats with traumatic hemorrhagic shock

作　　者：应盼 吴先龙[1] 杨志辉[1] 辛文伟 YING Pan;WU Xianlong;YANG Zhihui;XIN Wenwei(Department of Emergency,Taizhou First People′s Hospital in Zhejiang Province,Taizhou 318020,China)

机构地区：[1]浙江省台州市第一人民医院急诊科,浙江台州318020

出　　处：《中国现代医生》2021年第10期31-35,F0003,共6页China Modern Doctor

基　　金：浙江省基础公益研究计划项目(LGF19H150001)。

摘　　要：目的探讨乌司他丁对创伤失血性休克大鼠肺炎症介质及其信号通路miR-146a/TLR4/NF-κB的影响。方法将60只SD大鼠经股动脉放血制作休克模型,采用随机数字表法分为A、B、C三组,每组20只,其中A组不予复苏,B组休克后60 min给予醋酸钠林格液复苏,C组采用醋酸钠林格液联合乌司他丁复苏。采集大鼠复苏后肺组织,对肺组织中miR-146a、TNF-α、IL-1、IL-4、IL-6以及IL-10的mRNA水平予以检测,采用Western blotting对肺组织中TLR4、NF-κB蛋白相对表达量予以检测,对三组大鼠肺组织病理学变化予以观察。结果与A组、B组相比,C组大鼠miR-146a、IL-4、IL-10 mRNA水平提高,TNF-α、IL-1、IL-6水平下降,差异有统计学意义(P<0.05);三组大鼠肺组织TLR4、NF-κB蛋白表达水平相比,C组低于A组、B组,差异有统计学意义(P<0.05)。结论乌司他丁能够通过增强miR-146a表达复苏创伤失血性休克大鼠,对TLR4/NF-κB信号通路起到负反馈调控作用,维持促炎因子与抑炎因子平衡,对肺组织具有保护作用。Objective To investigate the impacts of ulinastatin on miR-146a/TLR4/NF-κB by pulmonary inflammatory mediators and the signaling pathway in rats with traumatic hemorrhagic shock.Methods A total of 60 SD rats were subjected to femoral artery bloodletting to establish shock models,and they were randomly divided into group A(n=20),group B(n=20)and group C(n=20).Among which,group A was not resuscitated,group B was resuscitated with sodium acetate Ringer solution 60 min after shock,and group C was resuscitated with sodium acetate Ringer solution combined with ulinastatin.The mRNA contents of miR-146a,TNF-α,IL-1,IL-4,IL-6 and IL-10 in the lung tissue of rats after resuscitation were detected.The relative expression of TLR4 and NF-κB protein in the lung tissue was detected by Western blotting,and the pathological changes of lung tissues of the three groups of rats were observed.Results Compared with group A and group B,the mRNA indexes of miR-146a,IL-4 and IL-10 in group C were increased,while the levels of TNF-α,IL-1 and IL-6 were decreased,with statistically significant differences(P<0.05).Compared with group A and group B,TLR4 and NF-κB protein expression levels in group C were significantly lower than those in group A and group B,with statistically significant differences(P<0.05).Conclusion Ulinastatin can resuscitate rats with traumatic hemorrhagic shock by enhancing the expression of miR-146a,play a negative feedback regulation role in TLR4/NF-κB signaling pathway,maintain the balance between pro-inflammatory factors and anti-inflammatory factors,and have protective efficacy on lung tissue.

关 键 词：乌司他丁 创伤失血性休克大鼠 炎症介质 MIR-146A TLR4/NF-κB通路 

分 类 号：R392.3[医药卫生—免疫学]