氟西汀对实验性抑郁症大鼠抑郁行为及海马神经元再生的影响

Effects of Fluoxetine Hydrochloride on the Depression Behavior and Regeneration of Hippocampus Neurons in Rats with Experimental Depression

目的观察盐酸氟西汀对实验性抑郁症大鼠抑郁行为的影响及海马神经元再生的影响,从而探讨抑郁症的发生机制及5-羟色胺(5-HT)再摄取抑制药治疗抑郁症的新型理论机制。方法采用长期不可预见性中等强度应激造成大鼠抑郁症模型。大鼠腹腔注射盐酸氟西汀前后行Open-field行为测定;应用免疫组织化学方法检测用药前后海马齿状回(DG)神经前体细胞标记物巢蛋白(nestin)的表达,并通过5-溴脱氧尿嘧啶尿苷(5-B rdU)观察DG神经前体细胞增殖所致的神经元再生。结果正常大鼠DG存在神经前体细胞,其中一些细胞处于分裂增殖状态。抑郁症大鼠DG神经前体细胞数目减少,而且其增殖明显减弱。应用盐酸氟西汀可显著改善抑郁症大鼠的抑郁行为,同时增加DG神经前体细胞的数目,其增殖也增强。结论抑郁症的发生可能与海马神经元再生减少有关,促进海马神经元再生可能是盐酸氟西汀治疗抑郁症的机制之一。

Objective To survey the effects of fluoxetine hydroehloride on the depression behavior and regeneration of hippocampus neurons in rats with experimental depression in order to probe into the mechanisms of the development of depression and the theoretical basis of the treatment of the disease with drugs that inhibit 5-HT reuptake. Methods The depression model in adult Wistar rats was set up by exposure of the animals to different unpredictable stresses of moderate intensity over a period of 21 days. The open-field behaviour test was adopted to study the depression behavior of the rats before and after the intraperitoneal injection of fluoxetine hydrochloride. Immunohistoehemieal technique was used to detect the expression of nestin the marker of the neural precursor cells of the hipocampal dentate gyrus （DG）. Neuron regeneration induced by the DG neural precursor ceils was observed with the use ofS-bromodeoxy-uridine（5-BrdU） . Results Neural precursor ceils were present in the DG of the normal rats and some of these ceils were in a state of division and regeneration. In rats with depression the DG neural precursor cells were decreased and attenuated in regeneration. Administration of fluoxetine hydrochloride was shown to dramatically improve the depression behavior, increase the number of DG neural precursor ceils and enhance the regeneration of these ceils in rats with depression. Conclusion The development of depression may be related to the decrease in the number of DG regenerating neurons. Promotion of the regeneration of DG neurons may be a novel idea with respect to the mechanism underlying the effect of fluoxetine hydrochloride in the treatment of depression.