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P2X7嘌呤受体在小鼠缺血后处理神经保护机制中的作用

Role of P2X7 purinoceptors in neuroprotective mechanism of ischemic postconditioning in mice.

作者信息

Bindra Chanpreet Singh, Jaggi Amteshwar Singh, Singh Nirmal

机构信息

Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala, 147002, Punjab, India.

出版信息

Mol Cell Biochem. 2014 May;390(1-2):161-73. doi: 10.1007/s11010-014-1967-9. Epub 2014 Feb 4.

Abstract

Cerebral ischemia-reperfusion (I-R) injury is one of the primary causes of ischemic stroke. Ischemic postconditioning (iPoCo) is evolving as an important adaptive technique to contain I-R injury. Some recent studies have shown neuroprotective effect of iPoCo. However, neuroprotective mechanism of iPoCo is not clear. So, the present study has been undertaken to investigate the possible role of P2X7 purinoceptors in neuroprotective mechanism of iPoCo in mice. Bilateral carotid artery occlusion for 12 min followed by R for 24 h produced a significant rise in cerebral infarct size and neurological severity score (NSS) along with impairment of memory and motor coordination. iPoCo, involving three episodes of 10-s carotid artery occlusion with intermittent R of 10 s applied just after ischemic insult of 12 min, produced a significant decrease in cerebral infarct size and NSS along with reversal of I-R-induced impairment of memory and motor coordination. iPoCo induced neuroprotective effects were significantly abolished by pretreatment with selective purinergic P2X7 receptor blocker Brilliant Blue G (40 mg/kg intraperitoneal). It may be concluded that neuroprotective effect of iPoCo probably involves in activation of purinergic P2X7 receptors.

摘要

脑缺血再灌注(I-R)损伤是缺血性中风的主要原因之一。缺血后处理(iPoCo)正逐渐成为一种控制I-R损伤的重要适应性技术。最近的一些研究表明了iPoCo的神经保护作用。然而,iPoCo的神经保护机制尚不清楚。因此,本研究旨在探讨P2X7嘌呤能受体在小鼠iPoCo神经保护机制中的可能作用。双侧颈动脉闭塞12分钟后再灌注24小时,导致脑梗死面积和神经严重程度评分(NSS)显著升高,同时伴有记忆和运动协调功能受损。iPoCo包括在12分钟缺血损伤后立即进行三次10秒的颈动脉闭塞,每次间隔10秒再灌注,可使脑梗死面积和NSS显著降低,并逆转I-R诱导的记忆和运动协调功能损伤。用选择性嘌呤能P2X7受体阻滞剂亮蓝G(40mg/kg腹腔注射)预处理可显著消除iPoCo诱导的神经保护作用。可以得出结论,iPoCo的神经保护作用可能涉及嘌呤能P2X7受体的激活。

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