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大蒜素对自发性高血压大鼠肠系膜动脉平滑肌细胞钙电流的作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2014年第4期
页码:
378-383
栏目:
基础研究
出版日期:
2014-04-25

文章信息/Info

Title:
Effects of garlcini on L-type calcium current of mesenteric artery smooth muscle cells in spontaneously hypertensive rats
作者:
王 瑞1; 王 萍2; 徐 斌3; 项国建3; 魏国良3; 杨 杰3; 李 泱3
(1.解放军451医院急诊科，陕西 西安 710054；
2.国防信息学院外军教研室，湖北 武汉 430010；
3.解放军总医院老年心血管病研究所，北京 100853)
Author(s):
WANG Rui1;  WANG Ping2;  XU Bin3;  XIANG Guo-jian3;  WEI Guo-liang3;  YANG Jie3;  LI Yang3
关键词:
大蒜素; 自发性高血压大鼠; 肠系膜动脉血管平滑肌细胞; 钙电流
Keywords:
SIRT3;  ischemia reperfusion;  arrhythmia;  oxidative stress
分类号:
R284.1
DOI:
-
文献标识码:
A
摘要:
目的:观察大蒜素(Gar)对自发性高血压大鼠(SHR)肠系膜动脉平滑肌细胞L-型钙电流(LCa,L)的影响。方法： 利用双酶-两步法消化得到单个大鼠肠系膜动脉血管平滑肌细胞，用全细胞膜片钳记录钙电流。在细胞池中灌流含Gar的细胞外液，观察药物对LCa,L的作用和门控机制及门控动力学参数的改变。结果： ①Gar对ICa,L的抑制效应呈浓度依赖性和电压依赖性特征。刺激电位0 mV时，200 μmol/L Gar可使 ICa,L峰值密度由(-8.4±0.4) pA/pF降低为(-6.1±0.3) pA/pF；②药物可使ICa,L半激活电压V1/2右移，半失活电压左移及失活后恢复动力学减慢等环节可减少通道的开放和重复开放，从而减少ICa,L峰值密度和窗口电流。结论： Gar可能通过减少细胞的钙电流发挥降压效应。
Abstract:
AIM:To investigate the role of cardiac deacetylase SIRT3 in ischemia/reperfusion (IR)-induced arrhythmias. METHODS: Twenty-four Sirt3 knockout (SIRT3 KO) mice and 24 wild-type (WT) mice were randomized into control group (Control, n=6), sham group (Sham, n=6), ischemia reperfusion group (I/R, n=6) and NAD+ treated I/R group (I/R+NAD, n=6). Wild-type and knockout mice were subjected to I (30 min)/R (2 h) and ECG was examined during I/R. NAD+ treatment was performed by intraperitoneal injection (7 days, 1 mg/kg/day) before I/R. At the end of the reperfusion period, arrhythmia score, reactive oxygen species (ROS) production, cardiac SIRT3 and Mn SOD levels were measured and analyzed. RESULTS: Compared with those in WT mice, cardiac SIRT3, Mn SOD and catalase expression decreased in SIRT3 KO mice. Arrhythmia was detected in SIRT3 KO mice under sham treatment. I/R triggered serious arrhythmia in WT mice and aggravated arrhythmia in SIRT3 KO mice (P<0.05). SIRT3 KO mice showed increased ROS production after I/R compared with WTI/R mice (P<0.05). NAD treatment significantly increased cardiac SIRT3 and MnSOD activity, inhibited ROS production and consequently suppressed I/R-induced arrhythmia in WT mice. However, NAD+ induced cardioprotctive effects were blunted in SIRT3 KO mice. CONCLUSION: Impairment of SIRT3 expression with subsequent ROS production plays an important role during I/R-induced arrhythmia and protection of SIRT3 activity may help prevent I/R-induced arrhythmia.

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备注/Memo

备注/Memo:
收稿日期：2013-12-04.基金项目：国家自然基金项目资助（81030002/H02，81170177）通讯作者：李泱，教授，主要从事高血压与心血管电生理研究 Email：liyangbsh@163.com 作者简介：王瑞，主任医师，硕士 Email：ruitao_1991@aliyun.cn
更新日期/Last Update: 2014-05-06