卡托普利对心肌梗死后心脏神经重构的影响

目的：探讨心肌梗死后早期应用血管紧张素转换酶抑制剂（ACEI）卡托普利对心脏自主神经重构的影响。方法：42只兔随机分为三组：卡托普利组（n=15）结扎冠状动脉前降支及卡托普利（10mg/kg·d）干预；对照组（n=15）结扎冠状动脉前降支；假手术组（n=12）穿线不结扎冠状动脉。术后8周行电生理检测，并用免疫组织化学及RT-PCR的方法观察心脏S100、GAP43及TH等神经标志物蛋白或基因表达水平的变化。结果：对照组在术后8周室性心律失常诱发率显著高于假手术组（P＜0.01），而卡托普利干预后其诱发率较对照组显著下降（P＜0.01）。对照组梗死灶周S100及GAP 43阳性神经纤维密度显著高于假手术组（P均＜0.01），且神经纤维分布紊乱；卡托普利组神经密度较对照组有所下降（P=0.07，P=0.13），但神经形态及分布状况更接近于假手术组。在非梗死左室游离壁，对照组神经密度显著高于假手术组（P均＜0.01），而卡托普利组与对照组差异无统计学意义（P＞0.05）。同时，对照组梗死灶周及非梗死左室游离壁TH mRNA表达水平显著高于假手术组（P＜0.01），而卡托普利组与对照组差异无统计学意义（P＞0.05）。结论：卡托普利可降低心肌梗死后室性心律失常的发生率，其机理可能与改善心脏神经纤维异常的形态及分布有关。

Effects of captopril treatment on cardiac neural remodeling in rabbits with artificial myocardial infarction

Objective： To investigate the effect of captopril, an angiotensin converting enzyme inhibitor, on cardiac neural remodeling after myocardial infarction. Methods： Forty-two rabbits were randomly divided into three groups: the captopril group, receiving ligation of the left anterior descending branch with captopril administration（10mg/kg·d）; the control group, receiving ligation of the left anterior descending branch; and the sham group, receiving thoracotomy without ligation. After 8 weeks, electrophysiological recordings were carried out and expressions of S100, GAP43 and TH were determined by immunohistochemical technique or RT-PCR. Results： The incidence of inducible VAs in the control group was obviously higher than that in the sham group (P＜0.01) after 8 weeks. However, it was significantly decreased after captopril treatment(P＜0.01). The densities of S100 and GAP43 positive nerve fibers were significantly greater in the control group than distribution in the control group was obviously diverse in contrast to the sham group. After captopril treatment, the densities dropped compared to the control group（P=0.07, P=0.13）. Otherwise, captopril normalized the inhomogeneous distribution and abnormal appearance of nerve fibers. The densities of S100 and GAP 43 positive nerve fibers at the non-infarct left ventricular free wall were decreased after captopril treatment, but no significant differences were found（P＞0.05）. Expression of TH mRNA in the control group was significantly increased compared with the sham group at both the infarct border and the non infarct left ventricle free wall. However, no significant differences were found between the captopril group and the control group. Conclusion： Captopril treatment is effective in reducing the occurrence of VAs in healed MI, partly by attenuating the heterogeneity of cardiac innervation and normalizing the appearance of cardiac nerve fibers.