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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

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.] [Ariticle in Chinese]

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, whileneuropeptide Y (NPY) participates in hippocampal dendrite growth. The present study was aimed to investigate the relationshipbetween NPY and nitric oxide synthase (NOS) in chronic unpredictable mild stress (CUMS)-induced depression. CUMS-induceddepression model was established in Sprague-Dawley rats. Intrahippocampal microinjections of NPY, NPY-Y1 receptor antagonistGR231118 and non-specific NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME) were respectively adopted by rat brainstereotaxic coordinates. The behavioral observations were conducted by sucrose consumption test, open field test and forced swimmingtest. The expressions of NPY, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) in hippocampuswere detected by immunohistochemistry. The results showed that, compared with the control group, rats receiving CUMS for 21 d orintrahippocampal microinjection of GR231118 showed a significant reduction in body weight and depression-like behavior, whichincluded reductions in sucrose preference, locomotor activity, rearing and grooming in open field test, and increased duration ofimmobility in forced swimming test. Moreover, the expression of NPY significantly decreased (P<0.01), while the expressions ofnNOS and iNOS increased obviously in the hippocampal dentate gyrus (DG) and CA3 regions (P<0.01). Intrahippocampal microinjectionsof NPY prevented the depression-like behavioral changes induced by CUMS and decreased the expressions of nNOS and iNOS

Key words: depression; hippocampus; chronic unpredictable mild stress; neuropeptide Y; nitric oxide synthase

收稿日期：2010-02-02　　录用日期：2010-04-16

通讯作者：安书成　　E-mail: shuchengan@snnu.edu.cn

引用本文：

廉婷, 安书成. 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[J]. 生理学报 2010; 62 (3): 237-246.

LIAN Ting, AN Shu-Cheng. [Antidepressant effect of microinjection of neuropeptide Y into the hippocampus is mediated by decreased expression of nitric oxide synthase.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (3): 237-246 (in Chinese with English abstract).