改善氧化应激平衡和逆转NET及HTT表达异常涉及文拉法辛的抗抑郁.DOCVIP

改善氧化应激平衡和逆转NET及5-HTT表达异常涉及文拉法辛的抗抑郁作用 胡小娅，费慧芝，蒋心惠，刘丹，邱红梅，汪丽佳，秦丽娟，周岐新(400016重庆，重庆医科大学药理学教研室) [摘要] 目的 探讨文拉法辛抗慢性轻度不可预见刺激所致大鼠抑郁症作用与氧化应激和海马NET（Norepinephrine transporter）、5-HTT（Serotonin transporter）表达的关系。方法 雄性SD大鼠80只，根据开场实验得分分为四组，即正常对照组(NG)、模型组（MG）、文拉法辛处理的正常对照组（VNG）和文拉法辛处理的模型组（VMG）。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；给药组每天给予文拉法辛(23.4mg/kg/d)，NG和MG组每天给予同体积溶剂。采用强迫游泳（force swimming）实验验证大鼠的抑郁行为，生物化学方法检测大鼠血清的丙二醛（MDA，Malondialdehyde）含量与超氧化物岐化酶（SOD，Superoxide dismutase）活性，实时定量RT-PCR分析海马5-HTT、NET的mRNA表达，Western-blot测定海马5-HTT、NET的蛋白表达。结果 相对于NG组，MG组大鼠在强迫游泳实验中的不动时间明显增加，血清MDA含量升高，SOD活性降低，海马5-HTT表达明显下降，而NET的表达显著升高。文拉法辛干预能阻遏CUMS诱导的上述变化；文拉法辛处理对正常对照大鼠的行为、MDA、SOD和NET及5-HTT表达无明显影响。结论 文拉法辛抑制CUMS诱导大鼠出现焦虑抑郁样行为的机制至少部分与其改善脑内氧化应激平衡，逆转5-HTT和NET异常表达有关。 [关键词] 文拉法辛；慢性轻度不可预见刺激；氧化应激；5-HTT；NET Improving oxidative stress response and reversing abnormal expression of hippocampus NET and 5-HTT involved in anti-depressive effect of venlafaxine Hu Xiaoya, Fei Huizhi, Jiang Xinhui, Liu Dan, Qiu Hongmei,Wang Lijia, Qin Lijuan，Zhou Qixin (Department of Pharmacology, Chongqing Medical Univercity, Chongqing, 400016, China) Objective To investigate if anti-depressive effect of venlafaxine was associated with improving oxidative stress and expression of hippocampus NET and 5-HTT in rat model induced by CUMS. Method 80 SD male rats were randomly divided into four groups: normal group(NG), model group(MG), venlafaxine-treated normal group (VNG), and venlafaxine-treated model group with (VMG). VNG and VMG were given venlafaxine 23.4mg/kg/d once daily, NG and MG were given the same volume solvent. Solitary condition with chronic mild unpredicted stress(CUMS) was taken to establish rat depression model. The force swimming was used to evaluate the behavior changes of experimental rats. The malondialdehyde (MDA) level and activity of superoxide dismutase (SOD) in serum were determined by biochemical methods. The expressions of NET and 5-HTT in hippocampus, were determined by Rea