猪冠状动脉微栓塞后心肌细胞凋亡与内质网应激相关蛋白CHOP表达的关系  

The relationship of myocardial apoptosis and endoplasmic reticulum stress-related protein CHOP in swine following coronary microembolization

作　　者：林崇强 刘涛 唐中力 刘阳春[4] 李浪[4] LIN Chong-qiang;LIU Tao;TANG Zhong-li;LIU Yang-chun;LI Lang(Department of Cardiovasolar Medicine,People＇s Hospital of Cenxi City in Guangxi Zhuang Autonomous Region,Cenxi543200,China;Department of Cardiovasolar Medicine,Minzu Hospital of Guangxi Zhuang Autonomous Region,Nanning530001,China;DepartmentofCardiovasolarMedicine,People＇sHospitalofDaoCountyinHunanProvince,DaoCounty 425300,China;Department of Cardiology,the First Affiliated Hospital of Guangxi Medical University,Nanning 530001,China)

机构地区：[1]广西壮族自治区岑溪市人民医院心血管内科,广西岑溪543200 [2]广西壮族自治区民族医院心血管内科,广西南宁530001 [3]湖南省道县人民医院心血管内科,湖南道县425300 [4]广西医科大学第一附属医院心血管内科,广西南宁530001

出　　处：《中国当代医药》2018年第12期9-13,共5页China Modern Medicine

基　　金：国家自然科学基金资助项目(81260042)

摘　　要：目的探讨猪冠状动脉微栓塞(CME)后心肌细胞凋亡与内质网应激相关蛋白C/EBP同源性蛋白(CHOP)表达的关系。方法将选取的50头小型猪随机分为Sham组和CME组,每组25头。采用介入法经冠脉内注入微栓塞球建立CME模型,Sham组经冠脉内注入等量生理盐水。根据术后观察时间点进一步分为3 h组、6 h组、12 h组、24 h组、48 h组,每组5头。应用超声心动图检测心功能,HE染色观察心肌组织病理学变化,苏木素碱性复红苦味酸(HBFP)染色检测心肌微梗死面积,缺口末端标记(TUNEL)法检测心肌细胞凋亡,Western blot检测心肌组织CHOP、Caspase-3蛋白表达。结果与相应Sham组比较,CME后各时间点心功能均不同程度下降(P<0.05),CME后12 h心功能下降最明显。CME后各时间点均可见多发局灶性微梗死心肌,以心内膜下及左心室为多,无大片坏死,各组间微梗死面积比较,差异无统计学意义(P>0.05)。与相应Sham组比较,CME组各时间点心肌细胞凋亡指数不同程度增加(P<0.05),CME后12 h心肌细胞凋亡达高峰。凋亡心肌细胞主要位于微梗死区及其边缘区。与相应Sham组比较,CME组各时间点CHOP、Caspase-3蛋白表达不同程度上调(P<0.05),呈动态变化,CME后12 h达高峰。结论 CME后CHOP蛋白表达上调可能参与内质网应激诱导的心肌细胞凋亡。Objective To investigate the relation of myocardial apoptosis and endoplasmic reticulum stress-related（CME） protein C/EBP homologous protein（CHOP） in swine following coronary microembolization.Methods Fifty swine were selected and randomly divided into the Sham group（n=25） and the CME group（n=25）.Five subgroups were assigned according to time points（3,6,12,24,48 h）,5 cases in each group.The CME model was established through injecting microspheres into the coronary artery,while swine in the Sham group received the same dose of normal saline instead.Cardiac function was measured with echocardiography.Histopathological changes were detected with HE.Microinfarction and apoptotic index were detected with hematoxylinbasic fuchsinpicric acid（HBFP） and TUNEL stainings,respectively.The expressions of CHOP and Caspase-3 proteins were determined with Western blot.Results Compared with the Sham groups,the cardiac function was decreased in varying degrees in the corresponding CME groups（P〈0.05）.The cardiac function of 12 h following CME was the worst.Microinfarction rather than massive necrosis was found each time points following CME,mainly located in left ventricle and subendocardial myocardium.The difference,however,was not statistically significant（P〉0.05）.Compared with the Sham groups,the apoptotic index in the corresponding CME groups were increased in varying degrees（P〈0.05）.It peaked 12 h following CME.Apoptotic cardiomyocytes were mainly located in microinfarct area and its border area.Compared with the Sham groups,CHOP protein expression in the corresponding groups following CME enhanced in varying degrees（P〈0.05）,showing dynamic changes.It peaked 12 h following CME.Conclusion CME induces cardiomyocyte apoptosis and cardiac dysfunction,in which enhanced CHOP and caspase-3 expression may be involved.

关 键 词：冠状动脉微栓塞 凋亡 C/EBP同源蛋白 内质网应激 

分 类 号：R543.3[医药卫生—心血管疾病]