沉默miR-26a减轻缺血/再灌注大鼠心肌损伤  

Silencing miR-26a alleviates myocardial ischemia-reperfusion injury in rats

作　　者：宫丹丹[1] 隋春兴[1] 石晨 李月 姜晓东[2] GONG Dan-dan;SUI Chun-xing;SHI Chen;LI Yue;JIANG Xiao-dong(Department of Cardiology,Dalian Municipal Central Hospital,Dalian 116033;Intensive Care Unit,the Second Hospital of Dalian Medical University,Dalian 116027,China)

机构地区：[1]大连市中心医院心内三科,辽宁大连116033 [2]大连医科大学附属第二医院重症医学科,辽宁大连116027

出　　处：《基础医学与临床》2021年第9期1285-1290,共6页Basic and Clinical Medicine

基　　金：辽宁省科学技术计划(20180550232);大连市医学科学研究计划(1712036)。

摘　　要：目的探讨微核糖核酸(miR-26a)对大鼠心肌缺血/再灌注损伤(I/R)的影响。方法将大鼠随机分为对照组(n=20)、I/R组(n=20)和siRNA组(n=20)。建立大鼠I/R模型前7 d,尾静脉注射miR-26a siRNA沉默内源性miR-26a。超声心动图检测心脏射血分数(EF%)和缩短分数(FS%);2,3,5-三苯基四唑氯化物(TTC)染色测定心肌梗死面积;HE染色法检测心肌细胞形态;TUNEL法检测心肌细胞凋亡水平;Western blot检测心肌组织中促凋亡蛋白Bcl-2相关X蛋白(Bax)和活性半胱天冬酶-3(caspase-3)和Rho/RhoA信号通路相关蛋白表达。结果I/R组心肌组织中miR-26a的表达明显高于对照组(P<0.05)。siRNA组心功能不全显著改善,大鼠的EF%和FS%均提高(P<0.05)。此外,siRNA组I/R所致的心肌梗死程度明显减轻,心肌梗死面积百分比由43.08%±2.43%减小到21.54%±1.82%(P<0.05)。siRNA组肌丝排列较整齐,心肌坏死程度较低,细胞水肿较I/R组明显减轻。siRNA组大鼠心肌细胞凋亡水平明显低于I/R组(P<0.05),Bax和caspase-3表达水平也明显下降(P<0.05)。miR-26a抑制可以显著降低I/R时Rho/RhoA信号通路蛋白表达(P<0.05)。结论miR-26a沉默可能通过降低Rho/RhoA信号通路蛋白表达抑制I/R所致心肌细胞凋亡。Objective To investigate the effect of miR-26a on myocardial ischemia-reperfusion(I/R)injury in rats.Methods Rats were randomly divided into control group(n=20),I/R group(n=20)and siRNA group(n=20).Seven days before the establishment of I/R model,miR-26a siRNA was injected into tail vein to silence endogenous miR-26a.Ejection fraction(EF%)and shortening fraction(FS%)were measured by echocardiography.The infarct size was measured by TTC.The morphology of cardiomyocytes was detected by HE staining.TUNEL assay was used to detect the level of cardiomyocyte apoptosis.Western blot was used to detect the expression of Bcl-2 related X protein(Bax),caspase-3 and Rho/RhoA signaling pathway related proteins.Results The expression of miR-26a in I/R group was significantly higher than that in control group(P<0.05).The EF%and FS%of siRNA group were significantly improved(P<0.05).In siRNA group,the severity of myocardial infarction caused by I/R was significantly reduced,and the percentage of myocardial infarction area was increased from 43.08%±2.43%to 21.54%±1.82%(P<0.05).In siRNA group,the myofilaments were arranged orderly,the degree of myocardial necrosis was low,and the cell edema was significantly alleviated compared with I/R group.The level of cardiomyocyte apoptosis in siRNA group was significantly lower than that in I/R group(P<0.05),and the expression levels of Bax and caspase-3 were also significantly decreased(P<0.05).Inhibition of miR-26a could significantly reduce the expression of Rho/RhoA signaling pathway protein during I/R(P<0.05).Conclusions miR-26a silencing may inhibit I/R-induced cardiomyocyte apoptosis by reducing expression of Rho/RhoA signaling pathway protein.

关 键 词：心肌缺血/再灌注损伤 miR-26a 心肌细胞 凋亡 

分 类 号：R364.1[医药卫生—病理学]