瑞波西汀抗大鼠抑郁作用与HPA轴功能和BDNF.doc

瑞波西汀抗抑郁作用的非转运体抑制机制研究 胡小娅，李 娜，费慧芝，王 涵，文 威，周岐新 （400016重庆，重庆医科大学药理学教研室） [摘要] 目的 探讨瑞波西汀抗大鼠抑郁作用与改善氧化应激平衡、HPA轴功能及BDNF表达关系。方法 60只雄性SD大鼠，随机分为对照组（NG）、模型组（MG）、灌胃给予瑞波西汀[0.7mg/（kg·d）]正常组(RNG)和灌胃给予瑞波西汀[0.7mg/（kg·d）]模型组（RMG）。采用孤养结合慢性轻度不可预见刺激（chronic unpredictable mild stress，CUMS）方法建立大鼠抑郁模型。以高架迷宫法、生物化学方法、放射免疫法免疫组化染色RT-PCR评价大鼠抑郁行为，检测皮质丙二醛（malondialdehyde，MDA）含量、超氧化物岐化酶（superoxide dismutase，SOD）和过氧化氢酶（catalase，CAT）的活性，血清corticosterone,CORT)和海马brain derived neurotrophic factor，BDNF）水平，以及下丘脑CRF）mRNA表达组大鼠进入开臂次数和明显闭臂的时间明显））nti-depressive effect of reboxetine on non-transporter inhibition Hu Xiaoya, Li Na, Fei Huizhi, Wang Han, Wen Wei, Zhou Qixin (Teaching and Research Section of Pharmacology, Chongqing Medical University, Chongqing 400016, China) [Abstract] Objective To study the relation of reboxetines anti-depression effect with oxidative stress balance, HPA axis function and BDNF expression. Methods Sixty male SD rats were randomly divided into normal controlgroup（），model groupreboxetine-treated normalgroup (RNG), and reboxetine-treated model group(RMG). reboxetine of 0.7mg/（kg·d）intragastric gavage. A rat depressive model was induced by chronic unpredictable mild stress（CUMS）. epressive behaviors of rats，Level of MDA and activities of SOD and CAT in cortex, serum CORT and hippocampus BDNF level, mRNA expressions of hippocampus BDNF and hypothalamus CRF， elevated plus maze (EPM), biochemistry, radioimmunity，immunohistochemical staining， and RT-PCR, respectively. Results The frequency for MG rats to enter the open arms and to explore downward significantly decreased, whereas the time for MG rats to stay in open arms was significantly shorten but the time to stay in close arms was significantly prolonged，compared with NG rats (P0.01, P0.05). The levels of MDA and CORT and CRF mRNA expression significantly increased, but the activities of SOD and CAT and BDNF mRNA and protein expressions significantly decreased in MG rats，compared with NG（P0.05 P0.01）Roboxetine treatment eff