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环孢霉素A干预钙调神经磷酸酶信号通路对持续心房起搏犬心房Cx40/Cx43表达的影响

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2009年第5期
页码:
606-610
栏目:
基础研究
出版日期:
2009-07-14

文章信息/Info

Title:
Effects of cyclosporin A on Cx40/Cx43 remodeling of atria in an atrial fibrillation canine model induced by atrial tachypacing
作者:
颜伟; 高磊; 黄亚; 陈琪; 张玉霄; 周圣华; 刘鹏; 卢才义
解放军总医院老年心血管病研究所，北京 100853
Author(s):
YAN Wei;  GAO Lei;  HUANG Ya;  CHEN Qi;  ZHANG Yu-xiao;  ZHOU Sheng-hua;  LIU Peng;  LU Cai-yi
Institute of Geriatric Cardiology, PLA General Hospital, Beijing 100853, China
关键词:
环孢霉素A; 心房颤动; 钙调神经磷酸酶; 心房重构; Cx40/Cx43
Keywords:
cyclosporine A;  atrial fibrillation;  calcineurin;  atrial remodeling;  connexin40/43
分类号:
R979.5
DOI:
-
文献标识码:
A
摘要:
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CsA干预组均表现为异质性增加，端端连接减少，侧侧连接增加。结论: CsA可减少ATP导致的Cx40/43表达的重构性变化，提示CsA可能具有一定的抑制心房重构的作用。
Abstract:
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.

参考文献/References

［1］ Lin CC, Lin JL, Lin CS, et al. Activation of the calcineurin-nuclear factor of activated T-cell signal transduction pathway in atrial fibrillation［J］. Chest, 2004, 126(6):1926-1932.

［2］ Shiroshita-Takeshita A, Brundel BJ, Lavoie J, et al. Prednisone prevents atrial fibrillation promotion by atrial tachycardia remodeling in dogs［J］. Cardiovasc Res, 2006, 69(4):865-875.

［3］ Bukowska A, Lendeckel U, Hirte D, et al. Activation of the calcineurin signaling pathway induces atrial hypertrophy during atrial fibrillation［J］. Cell Mol Life Sci, 2006, 63(3):333-342.

［4］ 严卉，陈君柱，朱建华，等. 缝隙连接蛋白在心房纤颤患者心房肌的表达及其信号转导途径［J］. 中华医学杂志, 2004, 84(3):209-213.

［5］ Polontchouk L, Haefliger JA, Ebelt B, et al. Effects of chronic atrial fibrillation on gap junction distribution in human and rat atria［J］. Am Coll Cardiol, 2001, 38(3):883-891.

［6］ Van der Velden HM, Ausma J, Rook MB, et al. Gap junctional remodelling in relation to stabilization of atrial fibrillation in the goat［J］. Cardiovasc Res, 2000, 46(3):476-486.

［7］ Kostin S, Kleina Q, Szalayb Z, et al. Structural correlate of atrial fibrillation in human patients［J］. Cardiovasc Res, 2002, 54(2):567-572.

［8］ Dupont E, Ko YS, Rothery S, et al. The gap junctional protein connexin40 is elevated in patients susceptible to postoperative atrial fibrillation［J］. Circulation, 2001, 103(6):842-849.

［9］ Tieleman RG, Crijns HJ. The second factor of tachycardia-induced atrial remodeling［J］. Cardiovasc Res, 2000, 46(3):364-366.

［10］Li We, Nagy JI. Connexin43 phosphorylation state and intercellular communication in cultured astrocytes following hypoxia and protein phosphatase inhibition［J］. Eur J Neurosci, 2000, 12(7):2644-2650.

［11］Mott JL, Zhang D, Freeman JC, et al. Cardiac disease due to random mitochondrial DNA mutations is prevented by cyclosporine A［J］. Biochem Biophys Res Commun, 2004, 319(4):1210-1215.

［12］Zhang D, Mott JL, Chang SW, et al. Construction of transgenic mice with tissue-specific acceleration of mitochondrial DNA mutagenesis［J］. Genomics, 2000, 69(2):151-161.

备注/Memo

备注/Memo:
收稿日期：2008-7-7.基金项目：国家自然科学基金项目资助(30570736/C03030201) 通讯作者：卢才义，主任医师，主要从事心脏电生理、冠心病方面研究Email:Cylu2000@sina.com.cn 作者简介：颜伟，主治医师，博士Email:yan_we@126.com
更新日期/Last Update: 2009-07-22