Physiology Research Center, Physiology Department, Faculty of Medicine Iran University of Medical Sciences, Tehran, Iran ; Astronautics Research Institute, Iranian Space Research Center, Tehran, Iran.
Physiology Research Center, Physiology Department, Faculty of Medicine Iran University of Medical Sciences, Tehran, Iran.
Iran J Basic Med Sci. 2015 Jan;18(1):14-21.
Morphine dependence (MD) potently protects heart against ischemia reperfusion (IR) injury through specific signaling mechanisms, which are different from the pathways involved in acute morphine treatment or classical preconditioning. Since opioid receptor density changes post cerebral ischemia strongly correlated with brain histological damage, in the present study, we tried to elucidate the possible role of opioid receptors in IR injury among morphine-dependent mice.
Accordingly, incremental doses (10 mg/kg/day to 30 mg/kg/day) of morphine sulphate were subcutaneously administered for 5 days before global brain ischemia induction through bilateral common carotid artery occlusion. Animals were received naloxone (5 mg/kg) or L-NAME (20 mg/kg) 30 min after the last morphine dose. Twenty four hr after the ischemia induction, Retention trial of passive avoidance test and western blot analysis were done. histological analysis (TUNEL and NISSL staining) performed 72 hr after ischemia.
MD improved post ischemia memory performance (P<0.01) and neuronal survival (P<0.001) and decreased apoptosis (P<0.05) in region I of hippocampus (CA1 region) in mouse. Treatment with naloxone or L-NAME abolished all MD aforementioned effects.
Results of the present study suggested that opioid receptors activation in the early hr post ischemia is crucial for MD-induced hippocampus tolerance against IR injury. Opioid receptor-dependent balance of NO production was another key factor in MD-induced protection. Further studies are required to determine the effect of MD on opioid receptor changes after ischemia and its correlation with MD-induced protection.
吗啡依赖（MD）通过特定的信号机制有力地保护心脏免受缺血再灌注（IR）损伤，这些机制与急性吗啡治疗或经典预处理涉及的途径不同。由于阿片受体密度在脑缺血后发生变化与脑组织损伤强烈相关，因此在本研究中，我们试图阐明阿片受体在 MD 依赖性小鼠的 IR 损伤中的可能作用。
因此，在通过双侧颈总动脉闭塞诱导全脑缺血前，连续 5 天每天皮下给予硫酸吗啡递增剂量（10mg/kg/天至 30mg/kg/天）。动物在最后一次吗啡剂量后 30 分钟接受纳洛酮（5mg/kg）或 L-NAME（20mg/kg）。在缺血诱导后 24 小时，进行被动回避测试保留试验和 Western blot 分析。缺血后 72 小时进行组织学分析（TUNEL 和 NISSL 染色）。
MD 改善了缺血后记忆表现（P<0.01）和神经元存活（P<0.001），并减少了海马区（CA1 区）I 区的细胞凋亡（P<0.05）。纳洛酮或 L-NAME 的治疗消除了 MD 上述所有作用。
本研究结果表明，缺血后早期阿片受体的激活对于 MD 诱导的海马体对 IR 损伤的耐受性至关重要。阿片受体依赖性 NO 产生平衡是 MD 诱导保护的另一个关键因素。需要进一步研究确定 MD 对缺血后阿片受体变化的影响及其与 MD 诱导保护的相关性。
