西拉普利对心房颤动犬内皮细胞功能及纤溶系统的影响

Effect of Cilazapril on endothelial cell function and fibrinolysis system in the canine atrial fibrillation models

目的研究血管紧张素转换酶抑制剂西拉普利对心房颤动(房颤)犬内皮功能和纤溶系统的影响。方法应用埋藏式高频心脏起搏器快速起搏心房建立房颤犬动物模型。实验分为未起搏组、单纯起搏组和起搏+西拉普利组。采用ISO NOP3005一氧化氮(NO)敏感电极测定心内膜NO含量;酶联免疫吸附双抗体夹心法测定血浆血管性血友病因子水平;Westernblot定量分析心房心肌纤溶酶原激活剂抑制物1(PAI1)和组织型纤溶酶原激活剂(tPA)蛋白表达;同时免疫组化检测蛋白表达位置。血浆PAI1和tPA含量采用酶联免疫吸附双抗体夹心法测定。结果西拉普利能显著增加房颤犬心内膜NO合成,降低血浆血管性血友病因子水平,同时显著减少心房肌PAI1蛋白表达和血浆PAI1含量,增加心房肌tPA蛋白表达和血浆含量。结论西拉普利能明显改善房颤犬内皮细胞功能,恢复纤溶系统平衡,可能对房颤的血栓前状态有益。

ObjectiveTo investigate the effect of cilazapril on endothelial cell function and fibrinolysis system in the canine atrial fibrillation(AF)models. MethodsAll canines were divided into three groups: (1)Control group, without atrial pacing; (2)Atrial pacing group, in which atrial fibrillation was established by rapid atrial pacing at 400 bpm for 6 weeks;(3) Atrial pacing together with cilazapril group, in which cilazapril was given before and after atrial pacing. Nitric oxide (NO) of atrial endocardium was measured with NO-specific microelectrode. The expression of plasminogen activator inhibitor-1(PAI-1) and tissue-type plasminogen activator(tPA)protein in atrium was determined by Western Blot analysis and immunohistochemical staining. Plasma levels of von Willebrand Factor (vWF), PAI-1 and tPA were analyzed by enzyme-linked immunoadsorbent assay. ResultsNO production from atrial endocardium was significantly increased in atrial pacing together with cilazapril group than atrial pacing group[(42.6±9.9)nmol/L vs(23.4±5.8)nmol/L , P<0.05], whereas the plasma levels of vWF were decreased [(75.4±12.8)% vs (125.9±20.6)%, P<0.05]. Compared to controls, the expression of atrium tPA protein in atrial pacing together with cilazapril group was significantly upregulated (4052±857 vs 1936±421, P<0.05) and PAI-1 protein was downregulated (2487±542 vs 3164±827, P<0.05). Cilazapril also significantly increased tPA antigen and decreased PAI-1 antigen in plasma. ConclusionCilazapril can favorably improve endothelial function and resume the balance of fibrinolysis system in AF, which might be of beneficial to hypercoagulated state in AF.