目的:观察钙调神经磷酸酶抑制剂环孢霉素A(CsA)对持续心房起搏(atrial tachypacing,ATP)模型犬心房中Cx40/Cx43表达分布的影响,探讨CsA抑制钙调神经磷酸酶信号通路(CaN)激活是否具有一定的抗心房重构的作用。方法:健康杂种犬18只,随机分为对照组(sham组)、心房快速起搏组(ATP组,植入固律型单腔起搏器,以400次/min持续起搏8周)及CsA干预组(在快速心房起搏组处理因素的基础上,喂食CsA 8周),每组6只。8周后,处死所有实验犬,采用免疫荧光染色法及蛋白印迹法,检测各组实验犬心房组织中Cx40/Cx43表达及分布的情况。结果:持续快速心房起搏8周,可导致犬左右心房中Cx40的表达明显增加(P〈0.01),但CsA干预组Cx40表达增加的程度明显小于ATP组(P〈0.05)。Cx40的分布方式,ATP组和CsA干预组均呈现出明显的异质性,均有端端连接减少,侧侧连接增加的现象。Cx43蛋白表达的趋势与Cx40不同:快速起搏8周后,犬左右心房组织中Cx43的表达均明显减少(P〈0.01),但减少的程度CsA干预组小于ATP组(P〈0.05)。Cx43的分布方式,ATP组及...
AIM: To observe the effects of cyclosporine-A(CsA) on the expression and distribution of atrial gap-junction protein Cx40/Cx43 in a canine model with atrial fibrillation(AF)-induced atrial tachypacing and to evaluate the inhibition of CsA on AF-induced atrial remodeling.METHODS: Eighteen healthy adult mongrel dogs(weighing 17-23.2 kg and ranging in age from 2 to 4 years) were divided into three groups: 1)sham group no pacemaker was implanted and no interventions;2)atrial tachypacing(ATP) group high-speed pacemaker was implanted and after 72 h postoperative recovery, the pacemaker was set to work at a rate of 400 bpm for 8 weeks ; 3 ) CsA group all procedures were the same as ATP group, but each canine was given CSA at a daily oral dose of 10 mg/kg. After 8 weeks, all canines were put to death and tissue samples were taken from the atrial free-wall. Expression and distribution of connexin40/connexin43 were detected with immunohistochemistry and Western blot methods. RESULTS: Compared with that in sham group, the expression of Cx40 protein in canine atrium significantly increased in ATP group (P 〈0. 01 ) and in CsA group (P 〈0. 05), but the changes in CsA group were much smaller than those in ATP group (P 〈 0. 05). Compared with that in sham group, expression of Cx43 decreased in both ATP and CsA groups (P 〈0. 01 ), but the changes in CsA group were much smaller than those in ATP group (P 〈 0. 05). The distribution heterogeneity of Cx40/43 increased with the increase of end-to-end conjunction and the decrease of side-by-side conjunction in both ATP and CsA groups. CONCLUSION: CsA inhibits the remodeling of Cx40/Cx43 and the atrial remodeling induced by atrial tachypacing in a canine model.