Nitric Oxide Participates in the Brain Ischemic Tolerance Induced by Intermittent Hypobaric Hypoxia in the Hippocampal CA1 Subfield in Rats
Nitric Oxide Participates in the Brain Ischemic Tolerance Induced by Intermittent Hypobaric Hypoxia in the Hippocampal CA1 Subfield in Rats
复制标题
一氧化氮参与大鼠海马 CA1 亚区间歇性低压缺氧诱导的脑缺血耐受
DOI：
10.1007/s11064-018-2593-9
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发表时间：
2018-09-01
影响因子：
4.4
通讯作者：
Zhang, Min
中科院分区：
文献类型：
--
作者：
Huang, Ya-Jie;Yuan, Yu-Jia;Zhang, Min
以往的研究表明，间歇性低压缺氧（IH）预处理可保护脑缺血后神经元的存活。然而，其机制仍有待阐明。本研究通过测定一氧化氮合酶（NOS）的表达和NO水平，探讨了一氧化氮（NO）在这一过程中的作用。雄性Wistar大鼠100只，随机分为假手术组、缺血再灌注组、缺血再灌注组。低氧预适应组大鼠模拟5000 m高原低压缺氧（PB= 404 mmHg，PO 2 = 84 mmHg），6 h/d，1次/d，共28 d。通过Pulsinelli创建的四血管闭塞建立全脑缺血。于缺血后第7天处死大鼠，硫堇染色进行神经病理学检查。于缺血后第2、7天检测海马CA 1区神经元型NOS（nNOS）、诱导型NOS（iNOS）的表达及NO含量。结果显示，全脑缺血可引起迟发性神经元死亡（DND），海马CA 1区nNOS和iNOS表达上调，NO含量增加。缺血预处理可减轻缺血引起的神经元损伤，抑制NOS表达和NO产生的上调。另外，设l-NAME +缺血组，观察抑制NO产生是否能减轻DND。预先给予1-NAME可减轻缺血引起的DND。提示IH预处理可能通过抑制脑缺血后NOS的过度表达和NO的含量而发挥脑保护作用。
Previous studies have shown that intermittent hypobaric hypoxia (IH) preconditioning protected neurons survival from brain ischemia. However, the mechanism remains to be elucidated. The present study explored the role of nitric oxide (NO) in the process by measuring the expression of NO synthase (NOS) and NO levels. Male Wistar rats (100) were randomly assigned into four groups: sham group, IH + sham group, ischemia group and IH + ischemia group. Rats for IH preconditioning were exposed to hypobaric hypoxia mimicking 5000 m high-altitude (PB= 404 mmHg, PO2= 84 mmHg) 6 h/day, once daily for 28 days. Global brain ischemia was established by four-vessel occlusion that has been created by Pulsinelli. Rats were sacrificed at 7th day after the ischemia for neuropathological evaluation by thionin stain. In addition, the expression of neuronal NOS (nNOS), inducible NOS (iNOS), and NO content in the hippocampal CA1 subfield were measured at 2nd day and 7th day after the ischemia. Results revealed that global brain ischemia engendered delayed neuronal death (DND), both nNOS and iNOS expression up-regulated, and NO content increased in the hippocampal CA1 subfield. IH preconditioning reduced neuronal injury induced by the ischemia, and prevented the up-regulation of NOS expression and NO production. In addition,l-NAME + ischemia group was designed to detect whether depressing NO production could alleviate the DND. Pre-administration ofl-NAME alleviated DND induced by the ischemia. These results suggest that IH preconditioning plays a protective role by inhibiting the over expression of NOS and NO content after brain ischemia.