作者：马国钤，杨茂东，刘演龙，张娅妮，冯亮，张毅恒，戴海龙，尹小龙

单位：

650051云南省昆明市，昆明医科大学附属延安医院心内科 云南省心血管疾病重点实验室 云南省心脏疾病临床医学中心 通信作者：戴海龙，E-mail：46944404@qq.com　 尹小龙，E-mail：yinxl001@gmail.com

Units：

Department of Cardiology/Key Laboratory of Cardiovascular Disease of Yunnan Province/Clinical Medicine Center for Cardiovascular Disease of Yunnan Province, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, China Corresponding author: DAI Hailong, E-mail: 46944404@qq.com; YIN Xiaolong, E-mail: yinxl001@gmail.com

关键词：

心肌梗死; 心肌缺血再灌注损伤; 猪; 滇南小耳猪; 心肌肌球蛋白结合蛋白C; 心肌肌钙蛋白Ⅰ;

Keywords：

Myocardial infarction; Myocardial ischemic reperfusion injury; Swine; Diannan small ear pig; Cardiac myosin binding protein-C; Cardiac troponin I

CLC：

DOI：

10.12114/j.issn.1008-5971.2022.00.284

Funds：

云南省科技厅科技计划项目〔2019FE001（-267）〕；昆明市卫生健康委员会卫生科研课题项目（2019-03-01-015）

摘要：

目的 分析心肌肌球蛋白结合蛋白C(cMyBP-C)在急性心肌梗死(AMI)、心肌缺血再灌注损伤模型猪中的表达及意义。方法 本实验时间为2020年6—12月。将9头试验用滇南小耳猪随机分为假手术组(开胸后打开心包，不结扎冠状动脉，n=1)、AMI组〔开胸后打开心包，结扎左前降支(LAD)中远段血管，n=4〕、心肌缺血再灌注损伤组(开胸后打开心包，结扎LAD中远段血管3 h后再开放，n=4)。观察各组滇南小耳猪手术前后心率及心电图表现、术后心脏组织病理切片，检测假手术组、AMI组术前及术后0.5、1.0、2.0、3.0、4.0、6.0、8.0、10.0、12.0、18.0、24.0 h心肌肌钙蛋白Ⅰ(cTnⅠ)、cMyBP-C水平，心肌缺血再灌注损伤组术前及术后0.5、1.0、2.0、3.0、3.5、4.5、5.5、6.5、7.5、9.5、11.5、13.5、15.5、21.5、27.5 h cTnⅠ、cMyBP-C水平。结果 假手术组无死亡发生；AMI组有1头滇南小耳猪死亡；心肌缺血再灌注损伤组有2头滇南小耳猪死亡。假手术组滇南小耳猪术前心率正常，节律规整，无ST段抬高，术后心率较术前增快；AMI组、心肌缺血再灌注损伤组滇南小耳猪结扎LAD中远段血管后开始出现心率加快，T波高尖、倒置，ST段抬高等ST-T段动态改变；心肌缺血再灌注损伤组滇南小耳猪开放LAD中远段血管后心率仍较快，ST段回落，T波倒置。术后心脏组织病理切片显示，假手术组心肌组织结构完整、心肌纤维条路清晰，细胞排列整齐规则、形态正常；AMI组及心肌缺血再灌注损伤组部分心肌纤维断裂及心肌细胞核溶解消失，细胞空泡样改变，大量炎症细胞浸润。假手术组手术前后cTnⅠ、cMyBP-C水平无明显变化。AMI组滇南小耳猪术后6.0、8.0、10.0、12.0、18.0、24.0 h cTnⅠ水平高于术前，术后1.0、2.0、3.0、4.0、6.0、8.0、10.0、12.0 h cMyBP-C水平高于术前(P<0.05)。AMI组滇南小耳猪cTnⅠ水平术前到术后4.0 h基本稳定，术后6.0 h开始逐渐升高，直至术后24.0 h；AMI组滇南小耳猪cMyBP-C水平术后1.0 h开始逐渐升高，术后6.0 h达高峰，之后逐渐降低。心肌缺血再灌注损伤组滇南小耳猪术后5.5、6.5、7.5、9.5、11.5、13.5、15.5、21.5、27.5 h cTnⅠ水平高于术前，术后1.0、2.0、3.0、3.5、4.5、5.5、6.5、7.5、9.5、11.5 h cMyBP-C水平高于术前(P<0.05)。心肌缺血再灌注损伤组滇南小耳猪cTnⅠ水平术前至术后4.5 h基本稳定，术后5.5 h开始逐渐升高，术后21.5 h达高峰，术后27.5 h略有下降；心肌缺血再灌注损伤组滇南小耳猪cMyBP-C水平术后1.0 h开始逐渐升高，术后4.5 h达高峰，之后逐渐下降，至术后13.5 h趋于稳定。结论 cMyBP-C水平在AMI及心肌缺血再灌注损伤发病早期即明显升高，且其升高早于cTnⅠ，其有巨大潜力成为早期诊断AMI、心肌缺血再灌注损伤的生物标志物。

Abstract：

【Abstract】　Objective To analyze the expression and significance of cardiac myosin binding protein-C (cMyBP-C) in acute myocardial infarction (AMI) and myocardial ischemia-reperfusion injury model pigs. Methods The experiment was conducted from June to December 2020. Nine Diannan small ear pigs were randomly divided into the Sham group (the pericardium was opened after thoracotomy without ligating the coronary artery, n=1) , AMI group [the pericardium was opened after thoracotomy and the middle and distal blood vessels of left anterior descending artery (LAD) were ligated, n=4] and myocardial ischemia-reperfusion injury group (the pericardium was opened after thoracotomy, the middle and distal blood vessels of LAD were ligated and reopened 3 hours later, n=4) . The heart rate and electrocardiographic manifestations before and after operation, the pathological sections of the heart tissue after operation of Diannan small ear pigs in each group were observed. The levels of cardiac troponin I (cTnI) and cMyBP-C in the Sham group and AMI group were detected before operation and at 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 18.0 and 24.0 h after operation, and the levels of cTnI and cMyBP-C in the myocardial ischemia reperfusion injury group were detected before operation and at 0.5, 1.0, 2.0, 3.0, 3.5, 4.5, 5.5, 6.5, 7.5, 9.5, 11.5, 13.5, 15.5, 21.5 and 27.5 h after operation. Results There was no death in the Sham group; one Diannan small ear pig in the AMI group died; two Diannan small ear pigs in the myocardial ischemia-reperfusion injury group died. In the Sham group, the heart rate of Diannan small ear pigs was normal before operation, the rhythm was regular, and there was no ST segment elevation, and the heart rate after operation was faster than that before operation. In the AMI group and the myocardial ischemia-reperfusion injury group, the Diannan small ear pigs began to experience rapid heart rate, sharp and inverted T waves, and ST-segment elevation after ligation of the middle and distal vessels of LAD. In the myocardial ischemia-reperfusion injury group, the heart rate of Diannan small ear pigs after opening the middle and distal vessels of LAD was still faster, the ST segment fell, and the T wave was inverted. Postoperative pathological sections of cardiac tissue showed that in the Sham group, the myocardial tissue structure was complete, the myocardial fibers were clear, the cells were neatly arranged, and the morphology was normal; some myocardial fibers were ruptured, myocardial cell nuclei were dissolved and disappeared, cells were vacuolated, and a large number of inflammatory cells were infiltrated in both the AMI group and the myocardial ischemia-reperfusion injury group. There was no significant change in the levels of cTnI and cMyBP-C before and after operation in the Sham group. In the AMI group, the levels of cTnI at 6.0, 8.0, 10.0, 12.0, 18.0 and 24.0 h after operation were higher than those before operation, and the levels of cMyBP-C at 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0 and 12.0 h after operation were higher than those before operation (P < 0.05) . The cTnI level of Diannan small ear pigs in AMI group was basically stable before operation to 4.0 h after operation, and it began to increase gradually at 6.0 h after operation until 24.0 h after operation. In the AMI group, the cMyBP-C level of Diannan small ear pigs began to increase gradually at 1.0 h after operation, reached a peak at 6.0 h after operation, and then gradually decreased. In the myocardial ischemia reperfusion injury group, the cTnI levels of Diannan small ear pigs at 5.5, 6.5, 7.5, 9.5, 11.5, 13.5, 15.5, 21.5 and 27.5 h after operation were higher than those before operation, and the levels of cMyBP-C at 1.0, 2.0, 3.0, 3.5, 4.5, 5.5, 6.5, 7.5, 9.5 and 11.5 h after operation were higher than those before operation (P < 0.05) . In the myocardial ischemia-reperfusion injury group, the cTnI level of Diannan small ear pigs was basically stable before operation to 4.5 h after operation, gradually increased at 5.5 h after operation, reached a peak at 21.5 h after operation, and decreased slightly at 27.5 h after operation. In the myocardial ischemia reperfusion injury group, the cMyBP-C level of Diannan small ear pigs began to increase gradually at 1.0 h after operation, reached a peak at 4.5 h after operation, and then gradually decreased, and stabilized at 13.5 h after operation. Conclusion The level of cMyBP-C is significantly increased in the early stage of AMI and myocardial ischemia-reperfusion injury, and its increase is earlier than cTnI. It has great potential to become a biomarker for early diagnosis of AMI and myocardial ischemia-reperfusion injury.

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