过表达miR-126对急性呼吸窘迫综合征模型大鼠右心功能的影响  

Effect of over-expressed miR-126 on right heart function in rats with acute respiratory distress syndrome

作　　者：龙光文[1] 张谦[1] 杨秀林[1] 吉春玲[1] 董裕康 LONG Guangwen;ZHANG Qian;YANG Xiulin;JI Chunling;DONG Yukang(Department of Emergency Medicine,Guizhou Provincial People's Hospital,Guiyang 550002,China)

机构地区：[1]贵州省人民医院急诊内科,贵阳550002

出　　处：《中国免疫学杂志》2022年第18期2182-2187,共6页Chinese Journal of Immunology

基　　金：贵州省科技计划项目(黔科合LH字[2016]7152);贵州省科技计划项目(黔科合基础[2017]1101)资助。

摘　　要：目的:探讨过表达miR-126对急性呼吸窘迫综合征(ARDS)大鼠右心功能的影响及可能机制。方法:将60只SD大鼠随机分成假手术组(Sham组)、模型组(Model组)、agomir阴性对照组(agomir-NC组)和miR-126 agomir组(agomir组),每组15只。采用颈部气管滴注LPS(10 mg/kg)法建立ARDS模型,术前24 h经尾静脉注射agomir-NC或miR-126 agomir。造模成功24 h后,行超声心动图检查评估大鼠右心功能,同时测定动脉血氧分压(PaO_(2))和氧合指数(OI);HE染色观察肺组织和右心组织病理学变化;ELISA法检测血清中心肌损伤标志物心肌肌钙蛋白Ⅰ(cTnⅠ)、肌酸激酶同工酶(CK-MB)和肌红蛋白(Mb)水平以及心肌组织中IL-1β和IL-18水平;qRT-PCR检测心肌组织中miR-126及NLRP3、caspase-1、ASC mRNA表达水平;Western blot检测心肌组织中NLRP3、ASC和caspase-1蛋白表达水平。结果:与Sham组比较,Model组大鼠肺组织和心肌组织病理损伤严重,三尖瓣环收缩期位移(TAPSE)、右心面积变化分数(FAC)和肺动脉加速时间(PAAT)显著减少,肺动脉收缩压(PASP)显著增加(P<0.01);动脉PaO_(2)和OI值以及心肌组织中miRNA-126表达水平显著降低(P<0.01),而血清中cTnⅠ、CK-MB和Mb含量、心肌组织中IL-1β、IL-18含量以及NLRP3、ASC、caspase-1的mRNA和蛋白表达水平均显著增加(P<0.01)。与Model组比较,agomir组大鼠肺组织和心肌组织病理损伤程度减轻,TAPSE、FAC和PAAT显著增加,PASP显著减小(P<0.01);动脉PaO_(2)和OI值以及心肌组织中miRNA-126表达水平显著升高(P<0.01),而血清中cTnⅠ、CK-MB和Mb含量,心肌组织中IL-1β、IL-18含量以及NLRP3、ASC、caspase-1的mRNA和蛋白表达水平均显著降低(P<0.01),而agomir-NC组大鼠以上各指标均无统计学意义(P>0.05)。结论:过表达miR-126可通过抑制NLRP3炎症小体活化,减轻炎症反应保护ARDS大鼠右心功能。Objective:To investigate the effect and possible mechanism of over expression miR-126 on right heart function in rats with acute respiratory distress syndrome(ARDS).Methods:Sixty SD rats were randomly divided into Sham group,Model group,agomir negative control group(agomir-NC group)and miR-126 agomir group(agomir group),with 15 rats in each group.ARDS model was established by cervical tracheal drip LPS(10 mg/kg).agomir-NC or miR-126 agomir were injected through tail vein 24 h before operation.After 24 h of successful modeling,echocardiography was performed to evaluate the right heart function of the rats.Determi⁃nation of arterial partial pressure of oxygen(PaO_(2))and oxygenation index(OI).Histopathological changes of lung tissue and right heart were observed by HE staining.Serum levels of cTnⅠ,CK-MB and Mb,as well as the IL-1βand IL-18 levels in myocardial tissue were detected by ELISA.The mRNA expression levels of miR-126,NLRP3,caspase-1 and ASC in myocardial tissues were detected by qRT-PCR.The protein expression levels of NLRP3,ASC and caspase-1 in myocardial tissue were detected by Western blot.Results:Compared with Sham group,the pathological damage of lung and myocardial tissues in Model group was serious.Tricuspid annulus systolic displacement(TAPSE),right heart area change fraction(FAC)and pulmonary artery acceleration time(PAAT)decreased significantly,while pulmonary arterial systolic blood pressure(PASP)increased significantly(P<0.01).The values of PaO_(2) and OI in arteries and the expression level of miR-126 in myocardial tissue were significantly decreased(P<0.01).The levels of cTnⅠ,CK-MB and Mb in serum,the levels of IL-1β,IL-18 and NLRP3,ASC and caspase-1 mRNA and protein in myocardial tissue were significantly increased(P<0.01).Compared with Model group,the pathological damage degree of lung tissue and myocardial tissue of agomir group was reduced.TAPSE,FAC and PAAT increased significantly,while PASP decreased significantly(P<0.01).The values of PaO_(2) and OI in arteries and the express

关 键 词：急性呼吸窘迫综合征 MIR-126 右心功能 NLRP3炎症小体 

分 类 号：R542.2[医药卫生—心血管疾病]