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

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2 h,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/dt_(max))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/dt_(max)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。

Protective effect of C1-esterase inhibitor against acute mvocardial ischemia-reperfusion iniurv in rats

Objective To investigate the protective effect of C1-esterase on the ischemia and reperfused 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,C1-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-1 (ICAM-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 diastolic pressure,CK,CK-MB significantly decreased.The infarct size and expression of ICAM-1, ICAM-1 mRNA were also decreased markedly.Conclusion C1-esterase inhibitor may inhibit the expression of ICAM-1 and so limit leucocyte aggregation,thus playing a protective effect against ischemia-reperfusion injury.