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

发布时间：2018-11-19 21:23

【摘要】：目的探讨文拉法辛抗慢性不可预见刺激所致大鼠抑郁症作用与氧化应激和海马去甲肾上腺素转运体(norepinephrine transporter,NET)、5羟色胺转运体(serotonin transporter,5-HTT)表达的关系。方法♂SD大鼠80只,根据开场实验得分分为4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)。采用孤养结合慢性不可预见刺激(chronic unpredictable stress,CUS)方法建立大鼠抑郁模型;给药组每天给予文拉法辛(23.4 mg·kg-1·d-1),NG和MG组每天给予同体积溶剂。采用强迫游泳(force swimming)实验评价大鼠的抑郁行为,生物化学方法检测大鼠血清的超氧化物岐化酶(superoxide dismutase,SOD)活性与丙二醛(malondialdehyde,MDA)含量,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,SOD活性降低,血清MDA含量升高,海马5-HTT表达明显下降,而NET的表达明显升高。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、SOD、MDA和5-HTT及NET表达无明显影响。结论文拉法辛抑制CUS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。
[Abstract]:Objective to investigate the effect of venlafaxine on depression induced by chronic unpredictable stimulation in rats and its relationship with oxidative stress and the expression of noradrenaline transporter (norepinephrine transporter,NET) and serotonin transporter (serotonin transporter,5-HTT) in hippocampus. Methods Eighty SD rats were divided into 4 groups according to the open field test scores: normal control group, (NG), model group, normal control group, (VNG) treated with (MG), venlafaxine and model group (VMG). Treated with venlafaxine, respectively. The rat model of depression was established by the method of solitary nourishment combined with chronic unpredictable stimulation of (chronic unpredictable stress,CUS, and the same volume of solvent was given daily in the administration group (23.4 mg kg-1 d-1), NG and MG group). The depressive behavior of rats was evaluated by forced swimming (force swimming) test, the activity of superoxide dismutase (superoxide dismutase,SOD) and the content of malondialdehyde (malondialdehyde,MDA) in serum of rats were detected by biochemical method, and the 5-HTT in hippocampus was analyzed by real-time quantitative RT-PCR. NET mRNA expression, Western blot was used to detect the expression of 5 HTT net protein in hippocampus. Results compared with NG group, the immobility time of MG group was significantly increased, the activity of SOD was decreased, the serum MDA content was increased, the expression of 5-HTT in hippocampus was obviously decreased, and the expression of NET was obviously increased in MG group. Venlafaxine could inhibit the changes induced by CUMS, but venlafaxine had no effect on the behavior, SOD,MDA, 5-HTT and NET expression of normal control rats. Conclusion the mechanism of venlafaxine inhibiting anxiety and depression-like behavior induced by CUS is at least partly related to the improvement of oxidative stress balance and reversal of abnormal expression of 5-HTT and NET in the brain.
【作者单位】：重庆医科大学药理学教研室;
【基金】：重庆市科委自然科学基金面上项目(No 2013JCYJA10040)
【分类号】：R749.4

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