Feng Rong-fang, Hu Yu-yan, Li Wen-bin, Liu Hui-qing, Li Qing-jun, Zhang Min
Department of Pathophysiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2009 May;25(2):182-5.
To explore the role of nitric oxide (NO) resulted from nNOS in the mGluR2/3 mediated-brain ischemic tolerance induced by cerebral ischemic preconditioning (CIP), the present study is undertaken to observe the influences of alpha-methyl-(4-tetrazolyl-phenyl) glycine (MTPG), an antagonist of mGluR2/3, on the expression of nNOS during the induction of the brain ischemic tolerance based on confirming the blocking effect of MTPG on the induction of the tolerance.
Thirty-six Sprague-Dawley rats, whose vertebral arteries were permanently occluded, were randomly divided into sham, CIP, ischemic insult, CIP+ ischemic insult, MTPG+ CIP and MTPG+ CIP+ ischemic insult groups. Thionin staining and immunohistochemistry were used for neuropathological evaluation and assay of nNOS expression in the hippocampal CA1 subregion of the rats.
The expression of nNOS showed moderate and extreme up-regulation in the CIP and ischemia groups, respectively, compared to the sham group. The preceded CIP blocked in certain extent the extreme up-regulation of nNOS induced by brain ischemia in CIP + ischemia group. Administration of MTPG via lateral cerebral ventricle 20 min before CIP blocked the up-regulation of nNOS induced by CIP, but had no influence on the pyramidal neuronal survival. While in the MTPG+ CIP+ ischemic insult group, the expression of nNOS was stronger than that in the MTPG + CIP group, and the up-regulation was accompanied with obvious delayed neuronal death. Discussion concerned illustrated that the relative intensive up-regulation of nNOS in this group might be attributed to brain ischemia other than MTPG.
NO resulted from nNOS participated the induction of mGluR2/3 mediated-brain ischemic tolerance as a downstream molecule of activation of mGluR2/3 during CIP.
为探讨nNOS产生的一氧化氮（NO）在代谢型谷氨酸受体2/3（mGluR2/3）介导的脑缺血预处理（CIP）诱导的脑缺血耐受中的作用，本研究在证实α-甲基-（4-四唑基-苯基）甘氨酸（MTPG）对脑缺血耐受诱导的阻断作用的基础上，观察mGluR2/3拮抗剂MTPG对脑缺血耐受诱导过程中nNOS表达的影响。
将36只椎动脉永久性闭塞的Sprague-Dawley大鼠随机分为假手术组、CIP组、缺血损伤组、CIP+缺血损伤组、MTPG+CIP组和MTPG+CIP+缺血损伤组。采用硫堇染色和免疫组织化学方法对大鼠海马CA1亚区进行神经病理学评价和nNOS表达检测。
与假手术组相比，nNOS表达在CIP组和缺血组分别呈中度和极度上调。预先的CIP在一定程度上阻断了CIP+缺血组脑缺血诱导的nNOS极度上调。在CIP前20分钟经侧脑室注射MTPG可阻断CIP诱导的nNOS上调，但对锥体神经元存活无影响。而在MTPG+CIP+缺血损伤组，nNOS表达强于MTPG+CIP组，且上调伴有明显的迟发性神经元死亡。相关讨论表明，该组nNOS相对强烈的上调可能归因于脑缺血而非MTPG。
nNOS产生的NO作为CIP过程中mGluR2/3激活的下游分子参与了mGluR2/3介导的脑缺血耐受的诱导。
