基于TLR4信号通路研究调控miR-217对脓毒症所致肺损伤模型大鼠的干预作用  

Inhibition effects of miR-217 on sepsis induced lung injury in rats based on TLR4 signaling pathway

作　　者：金丽[1] 邵峰[1] 徐建如[1] 葛志华[1] 沈寿引[1] 李晗 崔晓晖 刘亚琴[1] JIN Li;SHAO Feng;XU Jian-ru;GE Zhi-hua;SHEN Shou-yin;LI Han;CUI Xiao-hui;LIU Ya-qin(Emergency Department, the Third People's Hospital of Nantong City,Nantong226000,China)

机构地区：[1]南通市第三人民医院急诊科

出　　处：《海南医学院学报》2020年第1期6-11,共6页Journal of Hainan Medical University

基　　金：2019年度南通市卫生健康委员会科研立项课题(QA2019036)~~

摘　　要：目的探究基于Toll样受体4(TLR4)信号通路调控微小RNA-217(miR-217)对脓毒症所致肺损伤模型大鼠的作用。方法选择75只SD健康雄性大鼠(SPF级),随机分为正常组、假手术组、模型组、miR-217 mimics control组、miR-217 mimics组各15只,模型组、miR-217 mimics control组、miR-217 mimics组大鼠采用公认的盲肠结扎穿孔术(CLP)建立脓毒症肺损伤模型,miR-217 mimics control组、miR-217 mimics组尾部静脉注射10μL miR-217 mimics control、10μL miR-217 mimics,正常组、假手术组、模型组尾静脉注射等体积生理盐水。评价各组大鼠病理组织变化、肺湿重/干重(W/D)、动脉血气、TNF-α、IL-6、IL-1β、MPO、PMN细胞计数、miR-217、TLR4信号通路蛋白表达量。结果miR-217 mimics组病理学评分、W/D、pH、BE均低于miR-217 mimics control组,PaO2高于miR-217 mimics control组,差异有统计学意义(P<0.05)。miR-217 mimics组血清、肺泡灌洗液中TNF-α、IL-6、IL-1β、MPO水平低于miR-217 mimics control组,差异有统计学意义(P<0.05)。miR-217 mimics组肺泡灌洗液中蛋白含量、PMN细胞计数低于miR-217 mimics control组,差异有统计学差异(P<0.05)。miR-217 mimics组肺组织中miR-217表达量高于miR-217 mimics control组,肺组织中TLR4信号通路蛋白表达量低于miR-217 mimics control组,差异有统计学意义(P<0.05)。结论miR-217过表达通过抑制TLR4信号转导通路,阻断炎症反应,改善脓毒症所致的肺损伤,保护肺组织。Objective To investigate the effects of miR-217 on sepsis induced lung injury in rats.Methods A total of 75 healthy SD male rats(SPF grade)were randomly divided into normal group,sham operation group,model group,miR-217 mimicscontrol group,miR-217 mimics group with 15 rats in each group.CLP was used to establish sepsis lung injury models in model group,miR-217mimics control group and miR-217mimicsgroup.The miR-217 mimics control group and miR-217 mimicsgroup were injected with 10μLmiR-217 mimics controland miR-217 mimics,respectively through tail vein.While the same volume of saline were injected to the normal group,sham operation group,and model groupThe pathological changes,wet/dry weight of ling(W/D),arterial blood gas parameters,TNF-α,IL-6,IL-1β,MPO,PMN cell counts,expression level of miR-217 and TLR4 signal pathway protein were evaluated and compared.ResultsThe pathological scores,W/D,pH and BE of the mir-217 mimics group were all lower than that of the mir-217 mimics control group,while the PaO2 was higher than that of the mir-217 mimics control group,with statistically significant differences(P<0.05).The levels of TNF-α,IL-6,IL-1 and MPO in serum and alveolar lavage fluid of the mir-217 mimics group were lower than those of the mir-217 mimics control group,with statistically significant differences(P<0.05).The protein content and PMN cell count in the alveolar lavage fluid of the mir-217 mimics group were lower than that of the mir-217 mimics control group,with statistically significant differences(P<0.05).The expression level of mir-217 in the lung tissues of the mir-217 mimics group was higher than that of the mir-217 mimics control group,and the expression level of TLR4 signaling protein in the lung tissues of the mir-217 mimics control group was lower than that of the mir-217 mimics control group,with statistically significant differences(P<0.05).ConclusionOverexpression of miR-217 can inhibit TLR4 Signal transduction pathway,block inflammatory response,improve lung injury caused and protect lung t

关 键 词：TOLL样受体4 微小RNA-217 脓毒症 肺损伤 

分 类 号：R459.7[医药卫生—急诊医学] R563[医药卫生—治疗学]