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AMPK抑制剂P5499拮抗无钙预处理心肌保护作用(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2012年第1期
页码:
12-16
栏目:
基础研究
出版日期:
2012-02-25

文章信息/Info

Title:
Blunting effects of AMPK inhibitor P5499 on the cardioprotection of brief calcium depletion preconditioning
作者:
姚 远1; 毕生辉2; 冯建宇2; 时全星1; 张建英1; 周京军1; 裴建明1
(第四军医大学：1.生理学教研室，2.西京医院心血管外科，陕西 西安 710032)
Author(s):
YAO Yuan1;  BI Sheng-hui2;  FENG Jian-yu2;  SHI Quan-xing1;  ZHANG Jian-ying1;  ZHOU Jing-jun1;  PEI Jian-ming1
(1.Department of Physiology, School of Basic Medicine, 2.Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
腺苷酸活化的蛋白激酶; 无钙预处理; 心肌保护; 缺血/再灌注; 大鼠
Keywords:
AMPK;  calcium depletion preconditioning;  cardioprotection;  ischemia/reperfusion;  rats
分类号:
R542.2
DOI:
-
文献标识码:
A
摘要:
目的:观察腺苷酸活化的蛋白激酶(AMPK)抑制剂P5499对短暂无钙预处理心肌保护作用的影响。方法： 对健康SD雄性大鼠心脏行Langendorff离体灌流，实验全程记录心脏冠脉流量（CF）、左心室内压（LVP）、左室舒张末压(LVEDP)、室内压最大变化速率（±dp/dtmax）及心率（HR），并计算左室发展压（LVDP）和心率-压力乘积（RPP）评价心功能的变化。再灌注结束后，采用2、3、5-氯化三苯基四氮唑(TTC)染色法评价心肌梗死(MI)面积的变化。结果： 缺血/再灌注（I/R）后，心功能显著降低，CF明显减少（P<0.01），MI面积的比率为(39.6±1.49)%。短暂无钙预处理（CPC）可使LVEDP明显降低（P<0.05），CF、LVDP、±dp/dtmax及RPP均明显改善（P<0.01），MI面积显著缩小（P<0.01）。缺血前单独给予P5499对心功能、CF及MI面积无明显影响，但其可显著逆转CPC的心肌保护作用（P<0.01）。结论： AMPK可能是Ca2+预处理产生心肌保护信号的下游分子。
Abstract:
AIM:To evaluate the effect of P5499, an inhibitor of AMPK, on cardioprotection induced by brief calcium depletion preconditioning. METHODS: Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion. Left ventricular pressure (LVP), left ventricular end-diastolic pressure (LVEDP), maximum rates of increase and decrease in left ventricular pressure (±dp/dtmax), heart rate (HR) and coronary flow (CF) were monitored. Left ventricular diastolic pressure (LVDP) and rate pressure product (RPP) were calculated to evaluate myocardial performance. Triphenyltetrazolium chloride staining was used to measure the infarct size of myocardium. RESULTS: In the hearts subjected to global ischemia-reperfusion (I/R group), levels of LVDP, ±dp/dtmax, RPP and CF significantly decreased (P<0.01 vs. control group), and the infarct size was 39.6%±1.49%. Thirty-second perfusion with calcium-free KH solution (CPC group) before I/R reversed all the changes, level of LVEDP was decreased markedly (P<0.05 vs. I/R group), and levels of LVDP, ±dp/dtmax, RPP, CF and infarct size were significantly improved (P<0.01 vs. I/R group). P5499 administered before ischemia had no apparent effect on I/R-induced injury but significantly attenuated the cardioprotection of calcium depletion preconditioning (P<0.01 vs. CPC group). CONCLUSION: AMPK may mediate the protective effect of calcium preconditioning against I/R-induced injury.

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备注/Memo

备注/Memo:
收稿日期：2011-07-18.基金项目：国家自然科学基金项目资助（30971196）通讯作者：周京军，教授，主要从事心肌钙信号方面研究 Email:jjzhou71@yahoo.com 共同通讯作者：裴建明，教授，主要从事心血管生理学方面研究 Email:jmpei8@fmmu.edu.cn 作者简介：姚远，硕士生 Email:yaofaraway@yeah.net
更新日期/Last Update: 2012-02-14