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缺血预处理通过#beta#_(2)--肾上腺素受体保护心肌细胞收缩功能

吴芹 , 赵智, 孙红, 郝艳玲

徐州医学院生理学教研室.江苏,徐州 221002

摘要

该文旨在探讨缺血预处理(ischemic preconditioning, IP)对缺血/再灌注(ischemia/reperfusion, I/R)损伤心脏的保护机制，从细胞和受体水平研究#beta#_(2)--肾上腺素受体(#beta#_(2)--adrenergic receptor, #beta#_(2)--AR)是否参与了IP对I/R损伤心脏的保护作用。Sprague--Dawley大鼠随机分为单纯I/R组(对照组)、IP组、短暂异丙肾上腺素(isoproterenol, ISO)处理组、IP + ICI118551组、ISO + ICI118551组和ICI118551组，除单纯I/R组，其它各组大鼠经处理后均行缺血30 min，复灌30 min。离体大鼠心脏经不同处理后，停灌、复灌各30 min。记录心脏收缩期左心室内压上升的最大变化速率(+dp/dt_(max))、舒张期左心室内压下降的最大变化速率(--dp/dt_(max))及左心室内压差(left ventricular pressure，#DELTA#LVP，左心室收缩压--左心室舒张压)。测定冠状动脉流出液乳酸脱氢酶(lactate dehydrogenase, LDH)含量。进一步酶解分离心脏，得单个心室肌细胞，测定其存活率和收缩功能。结果显示，IP和ISO组±dp/dt_(max)、#DELTA#LVP较对照组增高；心肌细胞存活率和收缩幅度也显著升高；收缩时间(time--to--peak contraction, TTP)缩短；冠状动脉流出液LDH含量减少。选择性#beta#_(2)--AR拮抗剂ICI118551能阻断IP和ISO的作用。各组间心肌细胞舒张50%时间(time--to--50% relaxation, R_(50))和舒张100%时间(time--to--100% relaxation, R_(100))均无明显差异。结果提示，#beta#_(2)--AR可能在IP对I/R损伤心脏的保护作用中发挥重要作用。

关键词： 缺血预处理; 心肌细胞收缩功能; 肾上腺素能受体

#beta#_(2)--adrenoreceptor mediates the cardioprotection of ischemic preconditioning on myocardial contraction in rats subjected to ischemia/reperfusion injury

Wu Qin, Zhao Zhi, Sun Hong, Hao Yanling

Department of Physiology,Xuzhou Medical College.Xuzhou 221002,Jiangsu

Abstract

The presenr study aimed to investigate the role of #beta#_(2)-adrenoreceptor (#beta#_(2)-AR) in ischemic preconditioning (IP) in isolated rat heart model of ischemia/reperfusion (I/R). Sprague-Dawley rat hearts were quickly removed, mounted on Langendorff apparatus, and perfused with Krebs-Henseleit (KH) solution. After the initial stabilization period, the rats were randomly divided into 6 groups including control group (perfused for an additional 20 min), IP group (4 cycles of 5 min of ischemia followed by 5 min of reflow), isoproterenol (ISO) group (10 nmol/L of isoproterenol perfusion for 5 min followed by 5 min washout), IP + ICI118551 group (55 nmol/L ICI118551 perfusion for 5 min before and throughout IP), ISO + ICI118551 group (55 nmol/L ICI118551 perfusion for 5 min before and throughout ISO treatment), ICI118551 group (55 nmol/L ICI118551 perfusion for 20 min). After these treatments, all hearts were followed by 30 min no-flow ischemia and 30 min reperfusion. A computer-based electrophysiological recorder system was used to measure changes of the maximal rate of pressure increase in systole phase (+dp/dt_(max)), maximal rate of pressure decrease in diastole phase (-dp/dt_(max)), and difference of left ventricular pressure (#DELTA#LVP). Then cardiomyocytes from these hearts were isolated by 5 min of Ca~(2+)-free buffer perfusion and 25 min of collagenase perfusion. The ventricles were chopped and filtered. The myocytes were resuspended in KB buffer. The contraction and the viability of cardiomyocytes were measured. Lactate dehydrogenase (LDH) concentration in coronary effluent was assayed with assay kit. Both IP and ISO significantly increased the values of ±dp/dt_(max), #DELTA#LVP, the contraction and viability of cardiomyocytes, shortened the time-to-peak contraction (TTP), and decreased the release of LDH in coronary effluent. ICI118551, a selective #beta#_(2)-AR antagonist, blocked these effects. Either the time-to-50% relaxation (R_(50)) or the time-to-100% relaxation (R_(100)) had no significant differences in every group. Our results indicate that the cardioprotection of IP was mediated by #beta#_(2)-AR in isolated rat hearts subjected to I/R injury.

Key words: ischemic preconditioning;myocardial contraction;Adrenergic receptor

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引用本文：

吴芹 , 赵智, 孙红, 郝艳玲. 缺血预处理通过#beta#_(2)--肾上腺素受体保护心肌细胞收缩功能[J]. 生理学报 2008; 60 (3): 327-332.

Wu Qin, Zhao Zhi, Sun Hong, Hao Yanling. #beta#_(2)--adrenoreceptor mediates the cardioprotection of ischemic preconditioning on myocardial contraction in rats subjected to ischemia/reperfusion injury. Acta Physiol Sin 2008; 60 (3): 327-332 (in Chinese with English abstract).