MOTS-c肽对心肌缺血再灌注大鼠心肌损伤的保护作用  

Protective effect of MOTS-c peptide on myocardial injury in rats with myocardial ischemia reperfusion

作　　者：王毓 彭建业 朱明燕 Wang Yu;Peng Jianye;Zhu Mingyan(Dept of Laboratory,The Second Affiliated Hospital,Hengyang Medical School,University of South China,Hengyang 421001;Dept of Cardiovascular Medicine,The Second Affiliated Hospital,Hengyang Medical School,University of South China,Hengyang 421001)

机构地区：[1]南华大学衡阳医学院附属第二医院检验科,衡阳421001 [2]南华大学衡阳医学院附属第二医院心血管内科,衡阳421001

出　　处：《安徽医科大学学报》2024年第8期1405-1410,共6页Acta Universitatis Medicinalis Anhui

基　　金：湖南省自然科学基金面上项目(编号:2022JJ30518);湖南省卫生健康委科研计划项目(编号:202203012470)。

摘　　要：目的 探讨线粒体衍生肽MOTS-c对心肌缺血再灌注损伤(MIRI)大鼠心肌的保护作用,并阐明其作用机制。方法 将SD大鼠随机分成假手术组(sham组)、模型组(MIRI组)、MOTS-c组和MOTS-c+PGC-1α抑制剂SR-18292组(MOTS-c+SR-18292组),每组10只。采用冠状动脉前降支结扎法建立大鼠MIRI模型。各组大鼠于术前1 h及术后即刻经尾静脉给予MOTS-c肽(1 mg/kg)、SR-18292(20 mg/kg)和等体积浓度为1%的二甲基亚砜干预。术后24 h,采用氯化三苯基四氮唑(TTC)染色观察各组心肌梗死面积;苏木精-伊红(HE)染色观察各组心肌组织病理变化;原位末端标记法(TUNEL)染色检测各组心肌组织凋亡水平;酶联免疫吸附试验(ELISA)和生化试剂盒测定各组血清中心肌损伤标志物和氧化指标水平;实时定量聚合酶链反应(qRT-PCR)检测各组心肌组织线粒体DNA(mtDNA)相对拷贝数;Western blot检测各组心肌组织中线粒体生物合成相关蛋白表达水平。结果 与sham组比较,MIRI组大鼠心肌损伤严重,心肌组织梗死面积和凋亡水平升高(P<0.05),心肌组织mtDNA相对拷贝数降低(P<0.05),血清中CK-MB、LDH、cTnI及心肌组织中MDA含量升高(P<0.05),而SOD含量及PGC-1α、NRF-1、TFAM等蛋白表达水平降低(P<0.05)。与MIRI组比较,MOTS-c组大鼠心肌损伤明显改善,心肌组织梗死面积和凋亡水平降低(P<0.05),心肌组织mtDNA相对拷贝数升高(P<0.05),血清中CK-MB、LDH、cTnI及心肌组织中MDA含量降低(P<0.05),而SOD含量及PGC-1α、NRF-1、TFAM等蛋白表达水平升高(P<0.05)。与MOTS-c组比较,MOTS-c+SR-18292组大鼠心肌组织梗死面积和凋亡水平升高(P<0.05),心肌组织mtDNA相对拷贝数降低(P<0.05),血清中CK-MB、LDH、cTnI及心肌组织中MDA含量升高(P<0.05),而SOD含量及PGC-1α、NRF-1、TFAM等蛋白表达水平降低(P<0.05)。结论 MOTS-c肽可促进心肌细胞线粒体生物合成,抑制心肌细胞凋亡,改善MIRI大鼠心肌损伤,其机制可能与上调PGC-1α表达�Objective To investigate the protective effect of mitochondria-derived peptide MOTS-c on myocardial ischemia reperfusion injury(MIRI)in rats and elucidate its mechanism.Methods The SD rats were randomly divided into sham group,MIRI group,MOTS-c group and MOTS-c+PGC-1αinhibitor SR-18292 group(MOTS-c+SR-18292),with 10 rats in each group.The MIRI model was established by ligating the anterior descending branch of the coronary artery MOTS-c peptide(1 mg/kg),SR-18292(20 mg/kg)and equal volume concentration of 1%dimethyl sulfoxide were administered via tail vein at 1 h before operation and immediately after operation.At 24 h after surgery,TTC staining was used to observe myocardial infarction size.HE staining was used to observe the pathological changes of myocardial tissue.TUNEL staining was used to detect myocardial apoptosis.ELISA and biochemical kits were used to measure the levels of myocardial injury markers and oxidation indicators in serum of each group.The relative copy number of mtDNA in myocardial tissues was detected by qRT-PCR.The mitochondrial biosynthesis-related protein expression levels in myocardial tissues were detected by Western blot.Results Compared with sham group,MIRI group had serious myocardial injury,myocardial infarction size and increased apoptosis level(P<0.05).The mtDNA relative copy number in myocardial tissue decreased(P<0.05).The contents of CK-MB,LDH,cTnI in serum and MDA in myocardial tissue increased(P<0.05).SOD content and PGC-1α,NRF-1 and TFAM protein expression levels in myocardial tissue decreased(P<0.05).Compared with MIRI group,myocardial injury in MOTS-c group was significantly improved,myocardial infarction size and apoptosis level decreased(P<0.05).The mtDNA relative copy number in myocardial tissue increased(P<0.05).The contents of CK-MB,LDH,cTnI in serum and MDA in myocardial tissue decreased(P<0.05).The SOD content and the expression levels of PGC-1α,NRF-1 and TFAM in myocardial tissue increased(P<0.05).Compared with MOTS-c group,the myocardial infarction size and apo

关 键 词：MOTS-c肽 心肌缺血再灌注 心肌损伤 线粒体生物合成 过氧化物酶体增殖受体γ辅激活因子α 

分 类 号：R542.2[医药卫生—心血管疾病]