瑞波西汀抗抑郁作用的非转运体抑制机制研究  

Anti-depressive effect of reboxetine on non-transporter inhibition in rats

作　　者：胡小娅[1] 李娜[1] 费慧芝[1] 王涵[1] 文威[1] 周岐新[1] 

机构地区：[1]重庆医科大学药理学教研室,重庆400016

出　　处：《第三军医大学学报》2012年第19期1977-1980,共4页Journal of Third Military Medical University

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轴功能及脑源性神经营养因子(brainderived neurotrophic factor,BDNF)表达的关系。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[0.7 mg/(kg.d)]正常组(RNG)和灌胃给予瑞波西汀[0.7 mg/(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、免疫组化染色法和RT-PCR评价大鼠抑郁行为,检测皮质丙二醛(malondialdehyde,MDA)含量、超氧化物歧化酶(superoxide dismutase,SOD)和过氧化氢酶(catalase,CAT)的活性,血清皮质酮(corticosterone,CORT)和海马BDNF水平,以及下丘脑促肾上腺皮质激素释放因子(corticotropin releasing factor,CRF)mRNA表达。结果与NG组相比,MG组大鼠进入开臂次数和向下探究的次数明显减少(P<0.01),在开臂停留时间明显减少(P<0.05),而在闭臂停留的时间明显升高(P<0.05),皮质MDA含量明显升高(P<0.05),SOD和CAT活性显著下降(P<0.05),血清CORT浓度增加(P<0.05),海马BDNF mRNA表达和蛋白表达明显降低(P<0.01),下丘脑CRF mRNA表达显著增加(P<0.01)。瑞波西汀给予明显阻遏CUMS诱导的上述变化,但对正常组大鼠无显著影响。结论瑞波西汀的抗抑郁作用可能涉及其逆转机体氧化/抗氧化应激系统失衡,改善HPA轴功能,增加海马BDNF表达。study the relation of reboxetine＇ s anti-depression effect with oxidative stress balance, HPA axis function and brain derived neurotrophic factor （BDNF） expression. Methods Sixty male SD rats were randomly divided into normal control group （NG）, model group （MG）, reboxetine-treated normal group （ RNG）, and reboxetine-treated model group （RMG）. Reboxetine of 0.7μg/（ μg / d） was administered to RNG and RMG rats through intragastric gavage. A rat depressive model was induced by chronic unpredictable mild stress（CUMS）. Depressive behaviors of rats, level of MDA and activities of SOD and cata/ase （CAT） in cortex, serum corticosterone （CORT） and hippocampus BDNF level, mRNA expressions of hippocampus BDNF and hypothalamus corticotropin releasing factor （CRF）, were measured by 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 （P 〈0.01, P 〈0.05）. 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（P 〈 0.05, P 〈 0. O1 ）. Reboxetine treatment effectively prevented CUMS-induced the changes above in RMG rats, but failed to influence on RNG rats. Conclusion The anti-depression effect of reboxetine can improve the depressive behaviors of rats and up-regulate the BDNF expression in hippocampus by reversing the oxidative stress and anti-oxidative stress imbalance and improving the HPA axis function.

关 键 词：瑞波西汀 慢性轻度不可预见刺激 抗抑郁 氧化应激 HPA轴 脑源性神经营养因子 

分 类 号：R749.405[医药卫生—神经病学与精神病学] R965[医药卫生—临床医学]