远程缺血后处理联合奥美沙坦对自发性高血压大鼠心脏缺血再灌注损伤的保护作用  

The effect of remote ischemic postconditioning combined with Olmesartan against cardiac ischemia/reperfusion injury in spontaneously hypertensive rats

作　　者：鹿欣[1] 陈克彪[1] 张志东[1] 夏涛[1] 毕研玲[2] LU Xin;CHEN Kebiao;ZHANG Zhidong;XIA Tao;BI Yanling(Department of Cardiology,Taian City Central Hospital,Taian 271000,China;Department of Interventional Radiology yTaian City Central Hospital)

机构地区：[1]泰安市中心医院心脏外科,山东泰安271000 [2]泰安市中心医院介入放射科

出　　处：《潍坊医学院学报》2020年第5期331-334,共4页Acta Academiae Medicinae Weifang

基　　金：泰安市科技发展引导计划资助课题(项目编号:2017NS0123)。

摘　　要：目的研究远程缺血后处理(RIPOST)对自发性高血压大鼠(SHR)的心脏缺血再灌注(I/R)损伤的保护作用以及服用奥美沙坦(Olm)后对RIPOST保护作用的影响。方法 60只SHR随机分为6组:赋形剂-假手术组(vehicle-sham组)、赋形剂-缺血再灌注损伤组(vehicle-I/R组)、赋形剂-RIPOST组(vehicle-RIPOST组)、Olm-假手术组(Olm-sham组)、Olm-缺血再灌注损伤组(Olm-I/R组)、奥美沙坦-RIPOST组(Olm-RIPOST组)。Sham组:心脏左冠状动脉前降支(LAD)血管下穿线,不阻断LAD;I/R组:心脏LAD阻断血流40min后,复灌180min;RIPOST组:心脏复灌时,对大鼠左后肢使用止血带做3周期5min缺血/5min再灌注处理。测定各组大鼠左室肥厚指数、肌酸激酶(CK)、梗死面积、心律失常评分、HIF-1αmRNA表达、MiR-21表达以及MiR-210表达。结果 vehicle-I/R组与vehicle-RIPOST组中大鼠的梗死面积、心律失常评分和CK值差异无显著性。与Olm-I/R组相比,梗死面积和CK值在Olm-RIPOST组中显著降低(P<0.05)。与vehicle-sham组比较,HIF-1α,MiR-21和MiR-210的表达在Olm-sham组中显著降低(P<0.05)。与Olm-I/R组比较,HIF-1α,MiR-21和MiR-210的表达在Olm-RIPOST组中显著升高(P<0.05)。结论 RIPOST的保护作用在SHR中消失;服用Olm使大鼠心肌肥厚减轻,HIF-1α,MiR-21以及MiR-210的表达降低,从而减轻I/R损伤;服用Olm后恢复了RIPOST对SHR的保护作用,保护作用的恢复与HIF-1α,MiR-21和MiR-210 expression的表达升高有关。Objective To examine the effect of Remote ischemic postconditioning(RIPOST) in spontaneously hypertensive rats(SHR) and to determine whether chronic treatment with Olmesartan(Olm) could influence the effect of RIPOST.Methods Sixty SHR were randomly divided into six groups:vehicle-sham,vehicle-I/R,vehicle-RIPOST,Olm-sham,Olm-I/R and Olm-RIPOST.SHR in the sham subgroup underwent the same surgical procedures except that the suture passed under the left anterior descending coronary artery(LAD) without being tightened.LAD of SHR in the I/R subgroup was ligated for 40 min followed by a 180 min reperfusion.In the RIPOST subgroup,at the beginning of the reperfusion,the left hindlimb of SHR was subject to three cycles of 5 min of ischemia followed by 5 min of reperfusion.Left ventricular mass index,serum creatine kinase(CK),infarct size,arrhythmia score,HIF-1αmRNA expression,MiR-21 expression and MiR-210 expression were measured.Results The infarct size,arrhythmia score and CK were similar for the vehicle-I/R group and the vehicle-RIPOST group.However,the infarct size and CK were significantly decreased in the Olm-RIPOST group compared to the Olm-I/R group(P<0.05).Arrhythmia score was comparable for the Olm-RIPOST group and the Olm-I/R group.Moreover,HIF-1α,MiR-21 and MiR-210 expression were markedly down-regulated in the Olm-sham group compared to the vehicle-sham group and significantly up-regulated in the Olm-RIPOST group compared to the Olm-I/R group(P<0.05).Conclusion These results indicate that:(1)The protective effect of RIPOST is lost in vehicle treated SHR;(2)Chronic treatment with Olmesartan down-regulates HIF-1α,MiR-21 and MiR-210 expression and reduces hypertrophy,thereby limiting I/R injury;(3) Recovery of protective effect of RIPOST is related to the upregulation of HIF-1α,MiR-21 and MiR-210 expression.

关 键 词：远程缺血后处理 缺血再灌注损伤 奥美沙坦 自发性高血压大鼠 

分 类 号：R654[医药卫生—外科学]