诱导型一氧化氮合酶介导β淀粉样蛋白在体神经毒性

INDUCIBLE NITRIC OXIDE SYNTHASE INDUCES BETA-AMYLOID NEUROTOXICITY IN VIVO

目的 :探讨一氧化氮合酶 (NOS)及一氧化氮 (NO)在 β淀粉样蛋白 (Aβ)神经毒性和Alzheimer病 (AD)发病机制中的介导作用。方法 :应用行为学及病理学方法 ,观察海马内注射Aβ1-40 对大鼠Y迷宫学习记忆的影响及对局部神经元的损伤作用 ;观察特异性诱导型一氧化氮合酶 (iNOS)抑制剂胍氨酸 (AG)及特异性神经元型一氧化氮合酶 (nNOS)抑制剂 7 硝基吲哚 (7 NI)腹腔注射对海马内注射Aβ1-40 神经毒性的干预。结果 :海马注射Aβ1-40 后 ,大鼠Y迷宫学习记忆能力及海马局部神经元明显受损 ,特异性iNOS抑制剂AG能够阻止Aβ1-40 海马注射对大鼠学习记忆和局部神经元的损伤作用 ,而特异性nNOS抑制剂 7 NI无此干预效应。结论 :iNOS/NO参与了在体条件下对Aβ神经毒性的介导 。

Aim: To investigate the causative role of nitric oxide synthase (NOS) and nitric oxide (NO) in neurotoxicity of beta anyloid (Aβ) and the pathogenesis of Alzheimer's disease (AD). Methods: Using behavioral and neuropathological methods, we observed the effects of Aβ 1-40 injection into hippocampi on rats learning and memory in Y maze and on the neuropathology in hippocampi. The intervention by intraperitoneal administration of aminoguanidine (AG), a selective inducible NOS (iNOS) inhibitor, and 7 nitroindazole (7 NI), a selective neuronal NOS (nNOS) inhibitor, in the neurotoxicity of Aβ 1-40 was studied then. Results: The capability of acquisition and retrieval in Y maze and local neurons in hippocampus of the rats were impaired significantly after Aβ 1-40 injection. Intraperitoneal administration of AG, but not 7 NI, could prevent the damages caused by Aβ 1-40 injection above mentioned. Conclusion: iNOS/NO participates in the mechanisms of Aβ induced neurotoxicity and may play an important role in the pathogenesis of AD.