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

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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。

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	林崇强
	刘涛
	唐中力
	刘阳春
	李浪

关键词 ：冠状动脉微栓塞, 凋亡, C/EBP同源蛋白, 内质网应激

Abstract：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.

Key words： Coronary microembolization Apoptosis CHOP Endoplasmic reticulum stress

基金资助:国家自然科学基金资助项目（81260042）

作者简介: 林崇强（1982-），男，硕士研究生，主治医师，研究方向：冠心病的诊断及其防治研究

引用本文:

林崇强;刘涛;唐中力;刘阳春;李浪. 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[J]. 中国当代医药, 2018, 25(12): 9-13.
LIN Chong-qiang;LIU Tao;TANG Zhong-li;LIU Yang-chun;LI Lang. The relationship of myocardial apoptosis and endoplasmic reticulum stressrelated protein CHOP in swine following coronary microembolization. 中国当代医药, 2018, 25(12): 9-13.

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http://dangdaiyiyao.com/CN/ 或 http://dangdaiyiyao.com/CN/Y2018/V25/I12/9

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