Opioid receptor contributes to ischemic preconditioning through protein kinase C activation in rabbits
Opioid receptor contributes to ischemic preconditioning through protein kinase C activation in rabbits
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DOI：
10.1023/a:1006856124501
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发表时间：
1998-09-01
影响因子：
4.3
通讯作者：
Downey, JM
中科院分区：
文献类型：
--
作者：
Miki, T;Cohen, MV;Downey, JM
最近的研究报告称，阿片受体拮抗剂纳洛酮 (NAL) 可以阻断缺血预适应 (PC) 的保护作用。我们测试了阿片类激动剂是否可以在兔心脏中模拟 PC，这种保护是否涉及蛋白激酶 C (PKC) 激活，以及阿片类受体是否与其他 PKC 偶联受体协同作用。对兔心脏进行 30 分钟的冠状动脉闭塞，并再灌注 3（原位）或 2（体外）小时。通过用氯化三苯基四唑染色测定梗塞大小。在未经治疗的原位心脏中，38.5 +/- 1.6% 的风险区发生梗塞。 5 分钟缺血/10 分钟再灌注的 PC 将梗死率显着限制为 12.7 +/- 2.9% (p < 0.01)。 NAL 输注不会改变非 PC 心脏中的梗塞 (39.6 +/- 1.6%)，但会阻断 PC 一个周期的效果 (34.4 +/- 3.6% 梗塞)。然而，当 PC 通过 3 个缺血/再灌注周期扩增时，NAL 无法阻断心脏保护作用（9.9 +/- 1.4% 梗塞，与对照相比，p < 0.01）。吗啡也可以模拟缺血预处理，但剂量必须远高于临床使用剂量（3 毫克/千克）。在用吗啡 (0.3 μM) 预处理的离体心脏中，梗死率显着降低至 9.3 +/- 1.2%（p < 0.01 对比对照组的 32.0 +/- 3.1%）。吗啡的这种心脏保护作用可以被 PKC 抑制剂白屈菜红碱（30.4 +/- 2.6% 梗塞）或 NAL（34.0 +/- 2.6% 梗塞）阻断。白屈菜红碱和 NAL 本身都不能改善非 PC 心脏的梗塞。 NAL 不能阻断离体心脏中 PC 的一个周期的保护，表明内源性阿片类药物的产生可能需要完整的神经支配。因此，阿片受体与其他 PKC 偶联受体一样，参与兔心脏 PC 的触发。
Recent studies have reported that protection from ischemic preconditioning (PC) is blocked by the opioid receptor antagonist naloxone (NAL). We tested whether an opioid agonist could mimic PC in the rabbit heart, whether that protection involved protein kinase C (PKC) activation, and whether opioid receptors act in concert with other PKC-coupled receptors. Rabbit hearts were subjected to 30 min coronary occlusions and were reperfused for either 3 (in situ) or 2 (in vitro) h. Infarct size was determined by staining with triphenyltetrazolium chloride. In untreated in situ hearts 38.5 +/- 1.6% of the risk zone infarcted. PC with 5 min ischemia/10 min reperfusion significantly limited infarction to 12.7 +/- 2.9% (p < 0.01). NAL infusion did not modify infarction (39.6 +/- 1.6%) in non-PC hearts, but blocked the effect of one cycle of PC (34.4 +/- 3.6% infarction). NAL, however, could not block cardioprotection when PC was amplified with 3 cycles of ischemia/reperfusion (9.9 +/- 1.4% infarction, p < 0.01 vs. control). Morphine could also mimic ischemic preconditioning, but only at a dose much higher than would be used clinically (3 mg/kg). In isolated hearts pretreatment with morphine (0.3 mu M) significantly limited infarction to 9.3 +/- 1.2% (p < 0.01 vs. 32.0 +/- 3.1% in controls). This cardioprotective effect of morphine could be blocked by either the PKC inhibitor chelerythrine (30.4 +/- 2.6% infarction) or NAL (34.0 +/- 2.6% infarction). Neither chelerythrine nor NAL by itself modified infarction in non-PC hearts. NAL could not block protection from one cycle of PC in isolated hearts indicating that an intact innervation may be required for endogenous opioid production. Thus, opioid receptors, like other PKC-coupled receptors, participate in the triggering of PC in the rabbit heart.