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兴奋β3受体对快速心房起搏家兔心房肌细胞ICa,L的影响

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2013年第1期
页码:
6-009
栏目:
基础研究
出版日期:
2013-02-25

文章信息/Info

Title:
Effect of stimulating β3adrenergic receptors on Ltype calcium current in atrial myocytes of rapid atrial pacing rabbits
作者:
左瑞平; 于佳慧; 赵 静; 李为民
(哈尔滨医科大学第一临床医学院心血管内科，黑龙江 哈尔滨 150001)
Author(s):
ZUO Ruiping;  YU Jiahui;  ZHAO Jing;  LI Weimin
(Department of Cardiology, First Clinical College, Harbin Medical University, Harbin 150001, Heilongjiang, China)
关键词:
快速心房起搏; β3肾上腺素能受体; L型钙电流; 家兔
Keywords:
rapid atrial pacing;  β3adrenergic receptors;  Ltype calcium current;  rabbits
分类号:
R971.93
DOI:
-
文献标识码:
A
摘要:
目的:观察兴奋β3肾上腺素能受体（β3受体）对快速心房起搏(rapid atrial pacing，RAP)家兔心房肌细胞L型钙电流（ICa,L）的影响，为探索心房颤动（AF）的发病机制及治疗提供新的思路。方法： 35只20~25 kg家兔随机分组：1.离体部分：①假手术组（Sham组，n=7）：单纯开胸、安装起搏器不予起搏，1周后分离心房肌细胞，记录ICa,L（Sham组）。②手术组(n=7)：以600次/min RAP 1周后，分离心房肌细胞，记录ICa,L（RAP组）；向细胞中加入β1、β2受体阻滞剂Nadolol及β3受体激动剂BRL 37344（BRL），记录ICa,L（RAP+BRL组）；再加入β3受体特异性阻滞剂SR 59230A（SR），记录ICa,L（RAP+BRL+SR组）。2.在体部分：①RAP组（n=7）：单纯RAP 1周；②RAP+BRL组（n=7）：RAP后给予Nadolol及BRL 1周；③RAP+BRL+SR组（n=7）：RAP后给予Nadolol、BRL及SR 1周。测定各组心房肌一氧化氮（NO）、环-磷酸鸟苷（cGMP）的含量及cGMP依赖性蛋白激酶（PKG）蛋白的表达。结果： ①与Sham组相比，RAP组ICa,L明显减小（P<001）；②与RAP组相比，RAP+BRL组ICa,L明显减小（P<001），NO、cGMP的含量及PKG蛋白的表达明显增加（均为P<005）。③与RAP+BRL组相比，RAP+BRL+SR组ICa,L明显增大（P<001），NO、cGMP的含量及PKG蛋白的表达明显减少（P<001，P<001，P<005）。结论： 兴奋β3受体可激活NOcGMPPKG通路并同时减小RAP家兔心房肌细胞ICa,L。
Abstract:
AIM:To investigate the effect of stimulating β3adrenergic receptors (β3ARs) on Ltype calcium current (ICa,L) in atrial myocytes of rapid atrial pacing (RAP) rabbits. METHODS: Thirty seven rabbits (20-25 kg) were randomly divided: for ex vivo study in shamoperated group (sham group, n=7), thoracotomy was performed and pacemakers were implanted but not paced. Atrial myocytes were isolated after 1 week and ICa,L was recorded (sham group). In the operation group (n=7), rabbits were paced at 600 beats per minute for 1 week, atrial myocytes were isolated and ICa,L was recorded (RAP group). Atrial myocytes were then treated with β1, β2ARs blocker nadolol and β3ARs agonist BRL 37344 (BRL) and ICa,L was recorded (RAP+BRL group). Finally, atrial myocytes were incubated by β3ARs selective antagonist SR 59230A (SR) and ICa,L was recorded (RAP+BRL+SR group). For in vivo study: RAP group (n=7) with RAP for 1 week, RAP+BRL group (n=7) with RAP plus nadolol and BRL for 1 week, and RAP+BRL+SR group (n=7) with RAP plus nadolol, BRL and SR for 1 week. Nitric oxide (NO), cyclic guanosine monophosphate (cGMP) and the protein expressions of cGMPdependent protein kinases (PKG) were measured in each group. RESULTS: Compared with that in sham group, the density of ICa,L obviously decreased in the RAP group (P<0001) and compared with those in RAP group, the density of ICa,L obviously decreased (P<001) and the NO production, cGMP content and PKG protein expression obviously increased in RAP+BRL group (P<005). Compared with those in the RAP+BRL group, the density of ICa,L obviously increased (P<001) and NO production, cGMP content and PKG protein expression obviously decreased in RAP+BRL+SR group (P<0001, P<001, P<005). CONCLUSION: Activation of β3ARs decreases ICa,L in RAP rabbit atrial myocytes accompanied by stimulation of NOcGMPPKG signal pathway.

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备注/Memo

备注/Memo:
收稿日期：2012-05-30.基金项目：国家自然科学基金项目资助（81270252）；黑龙江省教育厅科学技术研究项目资助（11511308）通讯作者：李为民，主任医师，主要从事冠心病、心衰、房颤的诊治及相关机制研究 Email：lwm@54dr.com 作者简介：左瑞平，住院医师，硕士Email：zuozuole@yahoo.com.cn
更新日期/Last Update: 2013-03-20