Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India.
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India.
J Surg Res. 2014 May 1;188(1):349-60. doi: 10.1016/j.jss.2013.12.015. Epub 2013 Dec 18.
The present study was conducted to pharmacologically investigate the isoform-specific role of nitric oxide pathway in neuroprotective mechanism of ischemic postconditioning (iPoCo).
Bilateral carotid artery occlusion of 12 min followed by reperfusion for 24 h was used to produce ischemia- and reperfusion-induced cerebral injury in male Swiss mice. Memory was assessed using Morris water maze test. Degree of motor in-coordination was evaluated using inclined beam-walk test, rotarod test, and lateral push test. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Brain acetylcholinestrase activity, thiobarbituric acid-reactive species, nitrite/nitrate, and reduced glutathione levels were also estimated. Western blotting was performed to determine endothelial nitric oxide synthase (eNOS) expression.
Bilateral carotid artery occlusion followed by reperfusion produced significant rise in cerebral infarct size, acetylcholinesterase activity, and thiobarbituric acid-reactive species levels along with fall in nitrite/nitrate, and glutathione and eNOS expression levels. A significant impairment of memory and motor coordination was also noted. iPoCo consisting of three episodes of 10-s carotid artery occlusion and reperfusion significantly attenuated infarct size, memory impairment, motor in-coordination, altered biochemicals, and protein expression levels. iPoCo-induced neuroprotective effects were significantly abolished by L-NAME (a nonselective nitric oxide synthase inhibitor) and L-NIO (a selective eNOS inhibitor). However, aminoguanidine (a selective inducible nitric oxide synthase inhibitor) and 7-nitroindazole (a selective neuronal nitric oxide synthase inhibitor) did not modulate beneficial effects of iPoCo.
It may be concluded that nitric oxide pathway probably plays a vital role with specific involvement of eNOS in neuroprotective mechanism of iPoCo.
本研究旨在从药理学角度探讨一氧化氮通路在缺血后处理（iPoCo）神经保护机制中的同工酶特异性作用。
使用双侧颈总动脉闭塞 12 分钟，再灌注 24 小时的方法，在雄性瑞士小鼠中产生缺血再灌注引起的脑损伤。使用 Morris 水迷宫测试评估记忆。使用斜梁行走测试、转棒测试和侧推测试评估运动协调能力。使用氯化三苯基四氮唑染色测量脑梗死面积。还测定脑乙酰胆碱酯酶活性、硫代巴比妥酸反应性物质、亚硝酸盐/硝酸盐和还原型谷胱甘肽水平。通过 Western blot 测定内皮型一氧化氮合酶（eNOS）表达。
双侧颈总动脉闭塞再灌注后，脑梗死面积、乙酰胆碱酯酶活性和硫代巴比妥酸反应性物质水平显著升高，而亚硝酸盐/硝酸盐和谷胱甘肽及 eNOS 表达水平降低。记忆和运动协调能力也显著受损。由三个 10 秒颈总动脉闭塞和再灌注组成的 iPoCo 显著减轻了梗死面积、记忆损伤、运动不协调、生化改变和蛋白表达水平。L-NAME（非选择性一氧化氮合酶抑制剂）和 L-NIO（选择性 eNOS 抑制剂）显著阻断了 iPoCo 的神经保护作用。然而，氨基胍（选择性诱导型一氧化氮合酶抑制剂）和 7-硝基吲唑（选择性神经元型一氧化氮合酶抑制剂）不能调节 iPoCo 的有益作用。
一氧化氮通路可能在 iPoCo 的神经保护机制中发挥重要作用，特异性涉及 eNOS。
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