心肌肽素在小型猪急性心肌缺血再灌注中的作用

Cardioprotection of Cardiomyopeptidin in a Mini-pig Model of Acute Myocardial Ischemia-reperfusion Injury

目的利用小型猪急性心肌缺血再灌注的模型模拟临床急性心肌梗死患者内科再灌注治疗过程,探讨心肌肽素在小型猪急性心肌缺血再灌注中的保护作用及可能的作用机制。方法 12只小型猪分成单纯损伤组和治疗组,每组6只。X线下用球囊阻断冠状动脉左前降支血流造成心肌缺血;90 min后退出球囊,血流再通造成再灌注损伤。在心肌缺血60 min后,经静脉给予治疗组动物心肌肽素、单纯损伤组动物0.9%NaCl水溶液干预。分别在术前、用药结束和用药后24 h进行血清酶学及超声心动检查。用药24 h后,取出心脏进行TTC染色并测量梗死面积,切片行病理学检查、评分和原位凋亡检测。结果两组各有5只动物存活至实验终点,治疗组乳酸脱氢酶、肌酸激酶和肌酸激酶MB同工酶水平与单纯损伤组比较差异无统计学意义(P>0.05)。治疗组用药后24 h左心室舒张末容积较单纯损伤组增高,差异有统计学意义(P<0.05);两组的心肌梗死面积和损伤评分差异无统计学意义(P>0.05),治疗组的梗死区细胞凋亡较单纯损伤组明显减少(P<0.05)。结论用小型猪急性心肌缺血再灌注模型模拟急性心梗患者内科再灌注治疗,静脉输注心肌肽素可通过减少梗死区细胞凋亡保护心肌,但对于大面积、严重心梗患者,短时间、单独使用心肌肽素不能明显减小梗死面积和改善心功能。

Objective To observe whether Cardiomyopeptidin can protect myocardium in a mini-pig model of acute myocardial ischemia-reperfusion injury.Methods Twelve mini-pigs were used.A balloon was inflated in the left artery descending to block the blood and result in myocardial ischemia for 90 minutes.Then the balloon was deflated to induce reperfusion injury.Sixty minutes after the balloon inflation,Cardiomyopeptidin was administered by intravenous drop infusion in test group（n=6） while 0.9% sodium chloride was used in control group（n=6）.Before ischemia and at the end of and 24 hrs after administration,lactate dehydrogenase（LDH）,creatine kinase（CK）,and creatine kinase isoenzyme（CK-MB） in serum were detected,echocardiography was performed.Twenty-four hrs after administration,animals were sacrificed.Necrotic area was measured by triphenyhetrazolium chloride（TTC） staining and histopathology was described and scored.Apoptosis was detected by TUNEL.Results Five mini-pig of each group survived.There was no statistical difference between the two groups（P0.05） in LDH,CK and CK-MB.The left ventricular end diastolic volume（LVEDV） of test group was increased and higher than the control group at 24 hrs after administration（P0.05）.There was no statistical difference（P0.05） between the two groups in the rate of infarction area to all myocardium area by TTC staining and the score of myocardial injury.There were fewer apoptotic myocardial cells in test group than in control group（P0.05）.Conclusion In a mini-swine model of acute myocardial ischemia-reperfusion injury,Cardiomyopeptidin may protect myocardium by decreasing myocardial cells went apoptosis.However,the infarction area doesn＇t be reduced and the function of heart doesn＇t be proved only by Cardiomyopeptidin in a short-term when the myocardial injury is severe.