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慢性压力超负荷早期兔左心室肌中层细胞电重构的动态变化

赵永辉, 崔长琮

西安交通大学医学院第一医院心内科，环境和疾病相关基因教育部重点实验室，西安 710061；河南省人民医院心内科，郑州 450003

摘要

我们以往的研究发现，慢性压力超负荷致心室肌细胞肥大过程中，中层细胞动作电位时程(action potential duration, APD)逐渐延长且易发生早期后除极(early after-depolarization, EAD)。在本实验中，我们应用全细胞膜片钳技术进一步观察 慢性压力超负荷早期兔左心室肌中层细胞电重构的动态变化，并探讨此变化的病理生理学意义。取新西兰兔64 只，随机 分为缩窄组和假手术组，采用肾上腹主动脉缩窄术制备兔左心室压力超负荷模型。分别在术后2 周和8 周采用胶原酶两步 消化法分离获取左心室中层单个心肌细胞，全细胞膜片钳技术记录中层细胞慢激活延迟整流钾电流(IKs)、瞬间外向钾电流 (Ito)及L 型钙电流(ICa-L)。结果显示，术后2 周，与假手术组比较，缩窄组中层细胞IKs 尾电流(IKs,tail)密度降低33.3%，Ito 密 度降低51.5%，ICa-L 密度无明显改变；术后8 周，与假手术组比较，缩窄组中层细胞IKs,tail 密度降低37.0%，Ito 密度降低 49.2%，ICa-L 密度仍无明显改变。上述结果提示，在慢性压力超负荷的早期，兔左心室肌中层细胞电生理特性即发生明显改变，表现为I Ks 和I t o 下调，导致APD 延长，可能与恶性心律失常发生有关。

关键词： 膜片钳技术; 心室重构; 离子通道

分类号：Q463

[Dynamic changes of electrical remodeling in midmyocardium of rabbit left ventricle during the early stage of chronic pressure-overload.] [Ariticle in Chinese]

ZHAO Yong-Hui, CUI Chang-Cong

Department of Cardiology, First Hospital and Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Medical School of Xi’an Jiaotong University, Xi’an 710061, China； Department of Cardiology, Henan Provincial People’s Hospital, Zhengzhou 450003, China

Abstract

In the previous study, we had found that the action potential duration (APD) of midmyocardial (M) cells was gradually prolonged and M cells were easier to produce early after-depolarization (EAD) in the rabbit left ventricle during the early stage of chronic pressure-overload. The present study was performed to investigate the dynamic changes and significance of ionic current remodeling in M cells of rabbit left ventricle during the early stage of chronic pressure-overload. Sixty-four New Zealand rabbits were randomly divided into constriction groups and sham groups. The rabbit models with chronic pressure-overload were prepared by partial constriction of suprarenal abdominal aorta at the site proximal 5-10 mm away from the left renal artery. At 2 and 8 weeks after operation, the single cardiomyocytes were isolated by enzymatic digestion method. The midmyocardium from the anterolateral free wall of left ventricle was obtained by removing the epicardial and endocardial surfaces. Whole-cell patch-clamp technique was used to record the slowly activating delayed rectifier potassium current (IKs), transient outward potassium current (Ito), L-type calcium current (ICa-L) of M cells. At 2 weeks after the constriction operation, compared with the sham group, IKs tail current (IKs, tail) and Ito densities of M cells from constriction group significantly decreased by 33.3% and 51.5%, respectively. There was no significant difference in ICa-L density between the two groups. At 8 weeks after operation, compared with the sham group, IKs,tail and Ito densities of M cells from constriction group significantly decreased by 37.0% and 49.2%, respectively. There was still no significant difference in ICa-L density between the two groups. These results suggest that during the early phase of chronic pressure-overload, the electrical remodeling of M cells in rabbit left ventricle has developed, representing as the downregulations of IKs and Ito that can lead to the prolongation of APD, which might be a risk factor for the occurrence of malignant arrhythmia.

Key words: patch-clamp technique; ventricular remodeling; ionic channel

收稿日期：2008-07-07　　录用日期：2009-02-25

通讯作者：赵永辉　　E-mail: zhaoyonghui2000@stu.xjtu.edu.cn

引用本文：

赵永辉, 崔长琮. 慢性压力超负荷早期兔左心室肌中层细胞电重构的动态变化[J]. 生理学报 2009; 61 (3): 217-222.

ZHAO Yong-Hui, CUI Chang-Cong. [Dynamic changes of electrical remodeling in midmyocardium of rabbit left ventricle during the early stage of chronic pressure-overload.] [Ariticle in Chinese] . Acta Physiol Sin 2009; 61 (3): 217-222 (in Chinese with English abstract).