海马微量注射神经肽Y通过抑制一氧化氮合酶改善大鼠抑郁样行为.pdfVIP

生理学报 Acta Physiologica Sinica, June 25, 2010, 62 (3): 237-246 237 研究论文 海马微量注射神经肽 Y 通过抑制一氧化氮合酶改善大鼠抑郁 样行为 廉婷，安书成* 陕西师范大学生命科学学院，西安 710062 摘 要: 本文旨在探讨在慢性应激性抑郁发生过程中海马神经肽Y (neuropeptide Y, NPY)和一氧化氮合酶(nitric oxide synthase, NOS) 的关系。建立慢性不可预见性温和应激(chronic unpredictable mild stress, CUMS)抑郁模型，大鼠海马定位并分别微量 注射NPY 、NPY-Y1 受体阻断剂GR231118 和NOS 抑制剂L -NAME ，测量、计算动物体重变化并通过糖水偏爱测试、旷 场和强迫游泳实验等方法检测大鼠行为，免疫组织化学方法检测海马内NPY 、神经元型NOS (neuronal nitric oxide synthase, nNOS)和诱导型NOS (inducible nitric oxide synthase, iNOS) 的表达。结果显示，与对照组相比，CUMS 组大鼠表现出明显 的抑郁样行为变化，且海马NPY 表达下降、NOS 表达显著升高；海马微量注射NPY 明显改善应激引起的抑郁样行为表 现，并降低海马NOS 表达；用GR231118 选择性阻断NPY-Y1 受体后，大鼠的行为学表现能力下降，海马NOS 表达升 高；而CUMS 以及GR231118 所导致的行为学表现能力下降的现象均可被海马微量注射L -NAME 所反转。以上结果表明， CUMS 引起海马NPY 表达下降，NOS 表达升高，NO 过量产生，导致抑郁发生；而NPY 通过NPY-Y1 受体抑制NOS 的 过量表达是NPY 抗抑郁的一个重要途径。 关键词：抑郁； 海马；慢性不可预见性应激；神经肽Y ； 一氧化氮合酶 中图分类号：Q189; R749.4 Antidepressant effect of microinjection of neuropeptide Y into the hippocampus is mediated by decreased expression of nitric oxide synthase LIAN Ting, AN Shu-Cheng* College of Life Science, Shaanxi Normal University, Xi’an 710062, China Abstract: Accumulating evidence indicates an important role of hippocampal dendrite atrophy in the development of depression, while neuropeptide Y (NPY) participates in hippocampal dendrite growth. The present study was aimed to investigate the relationship between NPY and nitric oxide synthase (NOS) in chronic unpredictable mild stress (CUMS)-induced depression. CUMS-induced depression model was established in Sprague-Dawley rats. Intrahippocampal microinjections of NPY, NPY-Y1 receptor antagonist GR231118 and non-specific NOS inhibitor N -nitro-L -arginine methyl ester (L -NAME) were respectively adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by sucrose consumption test, open field test and forced swim- ming test. The expressions of NPY, neuronal nitric oxide synthase (n