补体C1抑制剂对缺血心肌补体C3合成及炎性反应的影响

Effect of C1 inhibitor on the synthesis of C3 and inflammatory reaction in ischemic reperfused myocardium

目的观察补体1抑制剂对缺血再灌注大鼠心肌补体C3合成及炎症反应的影响。方法结扎大鼠的左前降支30 min,再灌注3 h、72 h形成缺血再灌模型,实验分为假手术组、NaCl组和C1INH组(每组15只),观察C1INH对心肌及血浆髓过氧化物酶(MPO)活性的影响,放射免疫法检测血浆肿瘤坏死因子α(TNF-α)及白细胞介素2(IL-2)水平的变化,RT-PCR法检测缺血心肌中C3 mRNA含量变化。结果与NaCl组比较,再灌注72 h后,C1INH组心肌MPO活性分别在再灌注3 h[(3.69±0.02)U/g vs(3.11±0.03)U/g]和72 h[(3.08±0.03)U/g vs(1.99±0.03)U/g]后减少,血浆MPO活性亦减少,差异具有统计学意义(P<0.05),血清TNF-α和IL-2水平3 h和72 h浓度均降低(P<0.05)。同时RT-PCR分析显示,C1INH组心肌C3 mRNA的含量明显减少(P<0.05)。结论 C1INH除了抑制补体系统的激活,还减少心肌组织炎性细胞的浸润,降低血浆炎症因子水平,抑制缺血心肌C3 mRNA的表达。

Objective To explore the effect of C1 inhibitor （C1INH） on the synthesis of C3 in ischemic myocardium and inflammatory reaction.Methods Rat heart ischemia/reperfusion injury was induced by occluding the left anterior descending coronary artery for 30 min and reperfusion for 3 h or 72 h.The rats were divided into the C1 inhibitor group,NaCl group and sham operated group.The activity of myeloperoxidase （MPO） in myocardium and blood were measured.The level of TNF-α and IL-2 in blood were analyzed by radio-immunity method.The expression of C3 mRNA in ischemic myocardium was also observed.Results Compared with the NaCl group,C1INH reduced myeloperoxidase activity in myocardium,3 h [（3.69±0.02） U/g vs （3.11 ±0.03） U/g] and 72 h [（3.08±0.03） U/g vs （1.99±0.03） U/g],and in blood.The levels of TNF-α and IL-2 in blood were decreased.RT-PCR demonstrated a dramatic reduction in C3 mRNA expression of ischemic myocardium.Conclusion C1INH protects against I/R-induced myocardial injury via inhibition of C3 mRNA expression in ischemic myocardium and regulating the inflammatory reaction.