阿片受体在瑞芬太尼预适应对大鼠缺血后心脏保护中的角色

The role of opioid receptors in the protection of remifentanil preconditioning against heart post-ischemic injury in rats

目的探讨心脏上的阿片受体是否介导了瑞芬太尼预适应对缺血后心脏保护作用。方法麻醉开胸大鼠心脏缺血再灌注模型。分为对照组(CON),缺血预适应组(IPC)和瑞芬太尼预适应组(RPC);瑞芬太尼预适应的方法:在缺血再灌注前分别静注瑞芬太尼5 m in,停止5 m in共3个循环。三种阿片受体阻断剂Naltrindole(NTD,δ受体阻断剂,5 mg.kg-1)、nor-B inaltorph im ine(nor-BNI,к受体阻断剂,5 mg.kg-1)、CTOP(μ受体阻断剂,1 mg.kg-1),分别在RPC(NTD+RPC,BNI+RPC和CTOP+RPC组)和IPC(NTD+IPC,BNI+IPC和CTOP+IPC组)前静脉注射。观察指标包括:平均动脉压(MBP),心率(HR),记算收缩压心率乘积(RPP);缺血危险区(AAR),梗死区(IS)的体积,心肌梗死面积以IS/AAR来表示。结果在IS/AAR方面:NTD+RPC与CTOP+RPC与CON组之间无差别,与RPC有差别;nor-BNI+RPC与RPC及CON组之间都有差别;NTD+IPC和no-BNI+IPC与IPC组之间有差别,并且nor-BNI与CON组之间也有差别。结论μ,δ和κ-阿片受体介导了RPC对大鼠缺血后心脏的保护作用,μ-阿片受体的作用可能来至心脏之外的组织或器官。

Ahn To determine whether remifentanil preconditioning has Cardioprotection against ischemia and reperfusion induced injury via opioid receptor （OR） in rats. Method Male Sprague-Dawley rats of 300 - 350 g were anaesthetized and the chests were opened and hearts exposed via a left thoracotomy. They were randomly assigned to 12 groups：Control （CON, saline vehicle）, naltrindole （ NTD, 5 mg·kg^-1 iv. 10 rain before 30 min ischemia） ; CTOP （CTOP, 1 mg· kg^-1 iv. 10 min before ischemia） , nor-binaltorphimine （nor-BNI, 5 mg·kg^-1, iv. 15 min before 30 min ischemia） ; remifentanil preconditioning （RPC, 6 μg·kg^-1·min^-1 ） , ischemic preconditioning （ IPC ）, NTD ＋ RPC or NTD ＋ IPC （ naltrindole 5 mg· kg^-1 iv. 10 rain before RPC or IPC）, nor-BNI ＋ RPC or nor- BNI ＋ IPC （ nor-binaltorphimine 5 mg·kg^-1, iv. 15 min before RPC or IPC）, CTOP ＋ RPC or CTOP ＋ IPC （ CTOP 1 mg·kg^-1 iv. before RPC or IPC）. Infarct size （IS）, a percentage of the area at risk （AAR）, was determined by triphenyltetrazolium （TTC） staining. Results IPC and RPC markedly reduced IS/ AARfrom （52.7±1.8）% to （12.9±2.7）% and （ 16. 2± 2. 4 ） % , respectively. CTOP, a selective μ- OR antagonist, or NTD, a selective δ-OR antagonist, administered 10 min before remifentanil PC completely abolished, while nor-BNI, a selective κ-OR antago- nist, administered 15 min before RPC attenuated the cardioproteetive effect of RPC. In the group preconditioned with ischemia, blockade of δ-OR with NTD a- bolished, while blockade of κ-OR with nor-BNI attenuated the protection. Blockade of μ-OR with CTOP did not alter the cardioprotective effect of IPC. Conclusion The cardioprotective effect of RPC was abolished by all the three OR antagonist, CTOP, nahrindole and nor-binahorphimine, suggesting that this effect is mediated via μ-, δ-and κ-ORs. Part of the effect of RPC may be produced by μ-OR agonist activity outside the heart.