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吗啡降低大鼠远隔缺血预处理对心肌缺血再灌注损伤的阈值:阿片受体的作用。

Morphine reduces the threshold of remote ischemic preconditioning against myocardial ischemia and reperfusion injury in rats: the role of opioid receptors.

机构信息

Department of Anaesthesiology, Third Affiliated Hospital of Anhui Medical University, Hefei, China.

出版信息

J Cardiothorac Vasc Anesth. 2012 Jun;26(3):403-6. doi: 10.1053/j.jvca.2011.07.036. Epub 2011 Oct 7.

DOI:10.1053/j.jvca.2011.07.036
PMID:21982329
Abstract

OBJECTIVES

Opioid receptors mediate the cardioprotection of remote ischemic preconditioning (RIPC). The authors tested the hypothesis that morphine reduces the threshold of cardioprotection produced by RIPC.

METHODS

A randomized, prospective study.

SETTING

A university research laboratory.

PARTICIPANTS

Forty-five male Sprague-Dawley rats.

INTERVENTIONS

Anesthetized, open-chest, male Sprague-Dawley rats were assigned randomly to 1 of 7 treatment groups. RIPC1 and RIPC3 were, respectively, induced by 1 or 3 cycles of 5 minutes of femoral artery ischemia interspersed with 5 minutes of reperfusion. Morphine (MOR, 0.1 mg/kg) and the opioid receptor antagonist naloxone (NAL, 6 mg/kg) were administered 30 minutes before sustaining ischemia. MOR + RIPC1 and NAL + MOR + RIPC1 groups received the combination of MOR and RIPC1 in the absence or presence of NAL before coronary artery occlusion. Ischemia and reperfusion injury then were induced by 30 minutes of left coronary artery occlusion followed by 120 minutes of reperfusion.

MEASUREMENTS AND MAIN RESULTS

Infarct size, as a percentage of the area at risk, was determined by 2,3,5-triphenyltetrazolium staining. RIPC3 and the combination of MOR and RIPC1 groups significantly reduced the infarct size compared with the control group. RIPC1, MOR, and NAL did not affect infarct size. NAL pretreatment reversed cardioprotection of the combination of MOR and RIPC1 treatments.

CONCLUSIONS

MOR reduces the threshold of RIPC, and opioid receptors mediate this augmentative effect.

摘要

目的

阿片受体介导远程缺血预处理(RIPC)的心脏保护作用。作者检验了这样一个假设,即吗啡降低 RIPC 产生的心脏保护作用的阈值。

方法

一项随机、前瞻性研究。

设置

大学研究实验室。

参与者

45 只雄性 Sprague-Dawley 大鼠。

干预措施

麻醉、开胸雄性 Sprague-Dawley 大鼠随机分为 7 个治疗组之一。RIPC1 和 RIPC3 分别通过 5 分钟股动脉缺血与 5 分钟再灌注的 1 或 3 个循环来诱导。吗啡(MOR,0.1mg/kg)和阿片受体拮抗剂纳洛酮(NAL,6mg/kg)在缺血前 30 分钟给予。MOR+RIPC1 和 NAL+MOR+RIPC1 组在没有或存在 NAL 的情况下接受 MOR 和 RIPC1 的组合,然后在冠状动脉闭塞前进行。然后通过 30 分钟的左冠状动脉闭塞和 120 分钟的再灌注来诱导缺血和再灌注损伤。

测量和主要结果

通过 2,3,5-三苯基四唑染色确定梗死面积占危险区的百分比。RIPC3 和 MOR 和 RIPC1 组合组与对照组相比,梗死面积明显减小。RIPC1、MOR 和 NAL 不影响梗死面积。NAL 预处理逆转了 MOR 和 RIPC1 联合治疗的心脏保护作用。

结论

MOR 降低了 RIPC 的阈值,而阿片受体介导了这种增强作用。

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