阿片δ受体激动剂预处理延迟效应保护大鼠心肌的实验研究

Experiment Study of Opioid Receptor-Induced Delayed Preconditioning and Protection against Ischemic-reperfusion in Rat Heart

目的探讨以阿片δ受体激动剂能否诱导心脏缺血预处理的延迟保护效应及对大鼠心肌缺血-再灌注损伤的保护效果。方法大鼠随机分4组,A、B组以阿片δ受体激动剂DADLE预处理(2 mg/kg),C、D组注射生理盐水,24 h后4组都制成离体心脏,低温缺血3 h,复灌1 h。观测心功能、ATP等。其中B、D组在缺血前以优降糖阻止心肌ATP敏感性钾通道的开放。结果A左室压力变化最大速率恢复率和心肌ATP含量都高于B、C、D组,差异有显著性(P<0.01 orP<0.05),而B、C、D组间无明显差异。A组心肌丙二醛含量与CK-MB漏出活性明显低于B、C、D组(P<0.01 orP<0.05)。结论阿片δ受体激动剂可以诱导预处理的延迟效应,并减轻大鼠心肌的缺血-再灌注损伤,而ATP敏感性钾通道参与介导其效应的机制。

Objective To study the effect of the delayed preconditioning in rat heart triggered by opi- oid δ receptor and its protecting effect on rat heart ischemic-referfuion injury. Methods Wistar rats were randomly divided into groups A, B, C and D, and then opioid δ receptor, D-Ala^2-D-leu^5-enkephin（DADLE） was used to induce delayed preconditioning in A and B, while the rats in C and D were injected with saline. 24 h later, the hearts in all groups were subjected to 180 min of hypothermal ischemia, and 60 min of normothermial reperfusion with Langendorff-perfused isolated heart model, dp/dtmax of left ventricle, myocardial ATP and MDA content and CK-MB leakage were measured. Glibenclamide was used in groups B and D to inhibit ATP-sensitive potassium channels. Results The recovery rate of dp/dtmax in group A was better than that in groups B, C and D（P 〈0. 01 or P 〈0. 05）. Similarly, ATP content in A was higher than that in B, C and D（P 〈 0. 01）, and MDA content in A was much less than that in B, C and D（P 〈0.05 or P 〈0.01）, whereas there is no difference between B, C, D. Conclusion 33fis study showed that opioid δ receptor could induce delayed pre- conditioning, and ATP sensitive potassium channel may mediate this cardioprotection.