右美托咪定通过miR-21/PDCD4通路减轻心肌缺血再灌注损伤  

Dexmedetomidine ameliorates myocardial ischemia-reperfusion injury through miR-21/PDCD4 pathway

作　　者：易剑敏 李倩倩[1] 胡艳[1] 虞琦[1] YI Jian-min;LI Qian-qian;HU Yan;YU Qi(Department of Anesthesiology,the First Affiliated Hospital of Nanchang University,Nanchang JIANGXI 330000,China)

机构地区：[1]南昌大学第一附属医院麻醉科,江西南昌330000

出　　处：《中国新药与临床杂志》2023年第3期190-194,共5页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的探讨miR-21/程序性细胞死亡蛋白4(PDCD4)通路在右美托咪定(Dex)减轻大鼠心肌缺血再灌注(IR)损伤中的作用。方法健康雄性SD大鼠24只,随机分为假手术组、模型组、Dex组和Dex+agomiR-21(miR-21抑制剂)组。于制模前14日Dex组腹腔注射给予Dex 50μg·kg^(-1),Dex+agomiR-21组腹腔注射Dex 50μg·kg^(-1)+agomiR-2165 ng·kg^(-1),采用结扎冠状动脉左前降支30 min后恢复灌注120 min制模,假手术组穿线不结扎,采用小动物生物指标监测仪记录缺血前(T0)、缺血30 min(T1)、再灌注60 min(T2)和再灌注末(T3)时大鼠心功能指标。采用ELISA法测定IR心肌组织中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)、丙二醛(MDA)和超氧化物歧化酶(SOD)含量。Western blot法检测心肌组织中PDCD4的蛋白表达含量,q RT-PCR检测miR-21、PDCD4 mRNA表达。采用Target Scan预测miR-21和PDCD4的靶向关系。结果与假手术组相比,模型组T1、T2、T3时左室收缩压(LVSP)、心率(HR)、左室内压最大上升速率(+dp/dtmax)显著降低,左室舒张末压(LVEDP)和左室内压最大下降速率(-dp/dtmax)显著升高(P<0.05)。与模型组相比,Dex组T1、T2、T3时LVSP、HR、+dp/dtmax显著提高,LVEDP和-dp/dtmax显著降低(P<0.05);而Dex+agomiR-21组各指标与模型组相比无显著差异(P>0.05)。与假手术组相比,模型组TNF-α、IL-6、LDH、CK-MB和MDA含量显著增加(P<0.05),SOD显著降低(P<0.05),miR-21表达减少、PDCD4蛋白和mRNA表达增多(P<0.05)。与模型组相比,Dex组TNF-α、IL-6、LDH、CK-MB和MDA含量显著降低,SOD显著升高(P<0.05),miR-21表达增多,PDCD4蛋白和mRNA表达减少(P<0.05);而Dex+agomiR-21组各指标与模型组相比无显著差异(P>0.05)。Target Scan的预测结果显示PDCD4为miR-21的靶基因。结论Dex可增强IR损伤大鼠心功能,改善炎症和氧化应激,减轻心肌损伤,其机制可能与miR-21/PDCD4通路有关。AIM To investigate the role of miR-21/programmed cell death protein 4(PDCD4)pathway in dexmedetomidine(Dex)ameliorating myocardial ischemia-reperfusion(IR)injury in rats.METHODS Twenty-four healthy male SD rats were randomly divided into sham group,model group,Dex group and Dex+agomiR-21(miR-21 inhibitor)group.Dex 50μg·kg^(-1)and Dex 50μg·kg^(-1)+agomiR-2165 ng·kg^(-1)were intraperitoneally injected in the Dex group and Dex+agomiR-21 group 14 days before modeling.The left anterior descending coronary artery was ligated for 30 min and then the perfusion was restored for 120 min.The electrophysiological indexes of cardiac function were recorded before ischemia(T0),30 min of ischemia(T1),60 min of reperfusion(T2)and at the end of reperfusion(T3)using a small animal biological indicator monitor.The contents of tumor necrosis factor(TNF)-α,interleukin(IL)-6,lactate dehydrogenase(LDH)and creatine kinase isoenzyme(CK-MB),malondialdehyde(MDA)and superoxide dismutase(SOD)in myocardial tissue were determined by ELISA.Western blot was used to detect the protein expression of PDCD4 in myocardial tissue,and q RT-PCR was used to detect the mRNA expression of miR-21 and PDCD4.Target Scan was used to predict the targeting relationship between miR-21 and PDCD4.RESULTS Compared with the sham group,left ventricular systolic pressure(LVSP),heart rate(HR),+dp/dtmaxin the model group at T1,T2and T3decreased significantly,and left ventricular end diastolic pressure(LVEDP)and-dp/dtmaxincreased significantly(P<0.05).Compared with the model group,LVSP,HR,+dp/dtmaxin the Dex group at T1,T2and T3increased significantly,LVEDP and-dp/dtmaxdecreased significantly(P<0.05).However,there was no significant difference in all indexes between the Dex+agomiR-21 group and the model group(P>0.05).Compared with the sham group,the contents of TNF-α,IL-6,LDH,CK-MB and MDA increased significantly in the model group(P<0.05),SOD decreased significantly(P<0.05),miR-21 expression decreased,PDCD4 protein and mRNA expression increased(P<0.05).Compared wit

关 键 词：右美托咪定 心肌再灌注损伤 微RNAS 程序性细胞死亡蛋白 

分 类 号：R971.2[医药卫生—药品]