一氧化氮在海人酸所致神经毒性和记忆损害中的作用

Role of Nitric Oxide in Excitotoxicity and Memory Impairment Induced by Kanic Acid

目的 观察一氧化氮 (NO)在海人酸 (KA)对脑的兴奋毒性中的作用。方法 成年雌性 Wistar大鼠双侧尾核内注射 KA。术后 3个时间点测定一氧化氮合酶 (NOS)的活性 (即测定脑匀浆加入酶反应体系中产生的 NO2 -浓度 ) ,另一批大鼠经 KA注射后第 2～ 6天每天腹腔注射 10 mg/ kg L -硝基精氨酸甲酯 (L - NAME)或 2 5 m g/ kg 7-硝基吲哚 (7- NI)。术后 10 d起进行学习记忆行为试验。结果 尾核 NOS活性在术后 6～ 8h无明显变化 ,术后 3 d显著升高 ,术后 5 d仍轻度升高。L - NAME和 7- NI都能减轻 KA所致的被动回避反应记忆损害。只有 L - NAME能改善 KA所致的主动回避反应行为缺陷。结论 进一步表明 NOS激活和过量 NO可能介导 KA的兴奋毒性。早期多次使用 NOS抑制剂对 KA兴奋毒性引起的记忆缺陷有一定的改善作用。

The role of nitric oxide (NO) in excitotoxicity of kanic acid (KA) in the brain was investigated. Methods Adult female rats were bilaterally intra-caudate nucleus injected with KA.The nitric oxide synthase (NOS) was determined by measuring NO 2 - concentration produced from homogenized brain tissue in the enzyme response system at three time point after surgery.Another groups of rats were daily administrated (i.p.) L-NAME(10 mg/kg)or 7-NI(25 mg/kg)at 2nd to 6th day after intra-caudate KA injection.Behavioral tests for learning and memory were started at 10th day after surgery. Results NOS activity in caudate nucleus remained unchanged in 6～8 hours after surgery.It increased significantly in 3 days and slightly increased in 5 days after surgery.Both L-NAME and 7-NI ameliorated memory impairment induced by KA injection in passive avoidance response task.Only L-NAME improved KA-induced deficit in active avoidance reponse behavior. Conclusions This study gives further evidence that NOS activation and excessive NO may mediate KA-induced excitotoxicity.Early and repetitive use of NOS inhibitors shows some protective effect on memory deficit induced by KA excitotocicity.