心力衰竭大鼠心脏缝隙连接蛋白43的变化及厄贝沙坦的干预作用

Effect of Irbesartan on Connexin 43 Expression and Space-Remodeling in Left Cardiac Ventricles of Congestive Heart Failure Rats

目的观察压力超负荷所致心力衰竭大鼠心室肌中缝隙连接蛋白43表达的变化以及厄贝沙坦对心力衰竭时缝隙连接重构的干预作用。方法采用腹主动脉缩窄法建立大鼠心力衰竭模型,随机分为厄贝沙坦组和心力衰竭组,分别用厄贝沙坦(50 mg/kg)和安慰剂治疗,另设假手术对照组。术后16周用颈总动脉插管法测定心功能,用免疫印迹法检测心肌细胞缝隙连接蛋白43蛋白表达的变化,并以透射电镜观察缝隙连接空间重构的变化。结果心力衰竭大鼠心肌中缝隙连接蛋白43表达明显下调并出现空间重构,厄贝沙坦可明显上调缝隙连接蛋白43蛋白的表达并改善缝隙连接的空间重构。结论压力超负荷所致心力衰竭大鼠心室肌存在明显缝隙连接重构,这可能是心力衰竭时心肌电生理重构的机制之一,而此过程与血管紧张素Ⅱ的作用有关,血管紧张素受体拮抗剂厄贝沙坦可以明显改善心力衰竭时出现的缝隙连接重构。

Aim To determine the effects of irbesartan on gap junction remodeling and expression of connexin 43 （Cx43） in left cardiac ventricle of congestive heart failure （CHF） rats. Methods Aheartfailure model of experimentulpressure overload induced by surgical abdomiominal aortic stenosis in adult SD rats was used. The rats with heart failure were confinmed by measuring the hemodynamic parameters and divided randomly into the group treated with irbesartan （50 ms/ks ） and placebo. Sham-operated （PS） group rats served as negative controls after 16 weeks. Sixteen weeks later, gap junction remodeling in left cardiac ventricle of rats in sham-operated group, the irbesatan group, .and placebo group was characterized by immunoblotting and electron microscopy. Results Compared with Sham-operated group, the expression d Cx43 in left ventricles from failing hearts in the placebo group was decreased 25.7% （0.929±0.095 vs 1.250± 0.083, P 〈0.05）, the expression of Cx43 in left ventricles from irbesartan group increased to the same level of Sham-operated group. Electron microscopy of LV tissue revealed that in contrast to left ventricles myocytes from Sham-operated group, which showed Cx43 labeling largely confined to the intercalated disks, left ventricles myocytes from rats in placebo group showed dispersion of ptmctate Cx43 labeling over the entire cell surface. The proportion of Cx43 label at the intercalated disk decreased significantly. In rats from irbesartan group, the gap junction disorganization was markedly reduced. Conclusion In left ventricles from failing hearts, the expression of Cx43 decreased, while the expression d Cx43 in left ventricles from rats treated with irbesartan increased significantly. Meanwhile, Irbesartan can improve space-remodling d gap junction in failing hearts.