C1酯酶抑制剂对大鼠急性心肌缺血再灌注损伤的保护作用

摘要

Objective To investigate the protective effect of Cl-esterase on the ischemia and reper-fused rat myocardium and its possible mechanisms. Methods Forty-eight Wistar rats were randomly and evenly divided into four groups:sham-operated group,model control group,Cl-esterase inhibitor treated group and ischemic preconditioning group. ECG and hemodynamics were monitored during the period of ischemia and reperfusion. The activity of creatine kinase(CK) and CK-MB in the blood serum were measured and infarct size was determined. Immunohistochemical staining of the SABC method was used to measure the expression of intercellular adhesion molecule-KIC AM-1) and RT-PCR was used to determine the ICAM-1 mRNA expression in myocardium. Results After two hours of reperfusion,in comparsion with sham-operated group,the value of left ventricular systolic pressure(LVSP) and ±dp/dtmax were reduced and the activity of CK and CK-MB were markedly increased, and the expression of ICAM-1, ICAM-1 mRNA was also markedly increased in the model control group. Compared with model control group, in treated group and ischemic preconditioning group, LVSP, ±dp/dtmax increased, left ventricular end di-astolic pressure,CK,CK-MB significantly decreased. The infarct size and expression of ICAM-1, ICAM-1 mRNA were also decreased markedly. Conclusion Cl-esterase inhibitor may inhibit the expression of ICAM-1 and so limit leucocyte aggregation,thus playing a protective effect against ischemia-reperfusion injury.%摘要:目的 探讨C1酯酶抑制剂对大鼠心肌缺血再灌注损伤的保护作用及其可能机制.方法 将48只Wistar大鼠随机分为:假手术组、模型组、治疗组、预适应组,每组12只.建立急性心肌缺血再灌注损伤模型,模型组、治疗组、预适应组大鼠结扎左前冠状动脉30 min后再灌注2h,假手术组不结扎.检测血清肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)活性；检测各组大鼠心肌梗死范围；免疫组织化学法检测组织细胞间黏附分子1(ICAM-1)的表达及RT-PCR检测ICAM-1 mRNA的表达.结果 与假手术组比较,模型组大鼠左心室收缩压、左心室压力最大上升速率及最大下降速率(±dp/dtmax)明显降低,左心室舒张末压、CK、CK-MB、ICAM-1、ICAM-1 mRNA明显升高(P＜0.01)；与模型组比较,治疗组和预适应组大鼠左心室收缩压、±dp/dtmax明显升高(P＜0.01),左心室舒张末压、CK、CK-MB、ICAM-1、ICAM-1 mRNA明显降低(P＜ 0.05,P＜ 0.01),心肌梗死面积明显缩小(P＜0.01).结论 C1酯酶抑制剂可能通过阻断ICAM-1的表达,从而限制中性粒细胞聚集起到心肌保护作用.