【摘要】 兴奋性氨基酸、ＮＭ ＤＡ 受体和一氧化氮合酶／一氧化氮系统参与了缺氧性脑损伤的形成，急性重复缺氧则能通过缺氧预适应显著提高小鼠对缺氧的耐受性。本研究旨在观察外源离子型ＮＭ ＤＡ 受体激动剂天门冬氨酸和抑制剂氯氨酮对小鼠缺氧预适应的形成以及形成过程中ＮＯＳ在小鼠海马脑区表达的影响。取昆明小鼠随机分为天冬氨酸、氯氨酸和正常对照三组，分别腹腔注射天门冬氨酸（３ ｇ／ｋｇ）、氯氨酮（１００ ｍ ｇ／ｋｇ）和生理盐水（３ ｍ ｌ／ｋｇ）；分别造成各组动物急性重复缺氧１ 次和４ 次同时测定各组缺氧耐受时间，并采用ＮＡＤＰＨｄ 组织化学技术观察各组动物脑内ＮＯＳ的表达。结果表明：天冬氨酸和氯氨酮分别显著地缩短和延长了小鼠的标准耐受时间。缺氧１ 次后，各组动物脑内ＮＯＳ的表达增强，而４ 次缺氧后，由于缺氧预适应的形成ＮＯＳ的表达未继续增加而保持不变。三组动物在缺氧４ 次后脑内ＮＯＳ的表达依次为天门冬氨酸组＞ 正常对照组＞ 氯氨酮组。上述结果提示：ＮＯＳ的抑制可能有益于缺氧耐受，并可能是预适应的机制之一。离子型ＮＭＤＡ 受体的激活和抑制分别不利于和有利于缺氧预适应的形成，这也可能是因为受体的激活和抑制分别促进和抑制了ＮＯＳ在海马的表达。更多还原

【Abstract】 Excitatory amino acids, NMDA receptor, and nitric oxide synthase/nitric oxide(NOS/NO) system participate in brain damage. Acute repeated exposure to hypoxia significantly enhances mouse’s tolerance to hypoxia by preconditioning. The purpose of the present study was to observe the effect of extrinsic ionotropic NMDA receptor agonist(aspartate) and antagonist(ketamine) on hypoxic preconditioning of mouse brain and examine the effect of aspartate and ketamine on the expression of NOS in hippocampus. Kunming mice were divided randomly to three groups: ASP, NS and KET, and aspartate 3 g/kg, normal saline 3 ml/kg, ketamine 100 mg/kg were respectively administrated intraperitoneally. For each group, standard tolerance time in hypoxic preconditioning was determined and NOS expression after preconditioning was examined by NADPH diaphorase histochemical stain. NOS expression after the 1 st and 4 th hypoxic run with normal saline injection was also examind. Aspartate and ketamine respectively prolonged and shortened the standard tolerance time significantly. After the 1 st hypoxic run, NOS expression was increased, while after the 4 th run, NOS expression in the three groups were in the order of ASP>NS>KEF. The above results indicate that the inhibition of NO synthesis might be beneficial to hypoxic tolerance, and is one of the possible mechanism in preconditioning. The activation of ionotropic NMDA receptors is harmful while the suppression of ionotropic NMDA receptors is beneficial to the formation of hypoxic preconditioning, possibly because it promotes and inhibits NOS expression in hippocampus respectively.更多还原