氟西汀对抑郁模型大鼠海马CA1区少突胶质细胞作用的研究

Effects of fluoxetine on oligodendrocytes in CA1 of hippocampus in the CUS depression model of rats

摘要:

目的：探讨抗抑郁药物氟西汀对抑郁症慢性不可预知性应激（chronic unpredictable stress，CUS）模型大鼠海马CA1区内CNPase+少突胶质细胞的作用。方法：选用青年雄性Sprague Dawley（SD）大鼠（4~6周龄），随机分为对照组（12只）和模型组（38只），给予模型组大鼠连续4周的CUS干预。随后依据大鼠的糖水偏好百分比筛选出模大鼠，随机分为CUS组（12只）和CUS+fluoxetine组（FLX组）（12只），第5~7周CUS组和FLX组继续给予慢性应激，同时FLX组大鼠给予5 mg/（kg·d）氟西汀腹腔注射，对照组和CUS组给予等量生理盐水腹腔注射。干预结束后利用免疫组织化学方法结合现代体视学对大鼠海马CA1区CNPase+少突胶质细胞的数量进行精确的三维定量研究。结果：实验发现，CUS模型组大鼠的体质量（251.4±15.9） g较对照组（323.3±25.9） g明显下降（P=0.00），但与FLX组大鼠的体质量（257.9±22.7） g相比无差异（P=0.473）。CUS组大鼠的糖水偏好百分比（62.0±14.2）%明显低于对照组（89.2±4.8）%（P=0.000）及FLX组（78.2±12.8）%（P=0.020）。CUS组大鼠海马CA1区CNPase+细胞数量（18 650.7±1 812.0）明显低于对照组（33 606.9±4 471.4）（P=0.007）及FLX组（29 080.7±2 877.5）（P=0.042）。结论：大鼠海马CA1区内少突胶质细胞在抑郁症发病过程中可能起着重要作用，氟西汀治疗可防止抑郁症模型大鼠海马CA1区的CNPase+少突胶质细胞的丢失。本研究结果为探索新的抗抑郁策略提供了形态学基础。

Abstract:

Objective：To study the effects of anti-depressant-fluoxetine exposure on the CNPase+ oligodendrocytes in CA1 of hippocam－pus in the depressed rats which were induced by chronic unpredictable stress（CUS）. Methods：Male Sprague-Dawley（SD） rats were used，and were randomly divided into control group（n=12） and CUS group（n=３８） after the sucrose preference of the rats was normal and regular. Four weeks CUS and separation was used to build CUS depression model of rats. The sucrose preference was used to screen the depressed rats at the end of 4th week and 12 CUS-induced depressed rats were enrolled as CUS group and 12 as FLX group. The FLX group was treated with fluoxetine at dose of 5 mg/（kg·d） from the fifth week to seventh week. Meanwhile，the control group and the CUS group were treated with saline at the same dose. The CUS group and FLX group were continued exposure to CUS. The total number of CNPase+ oligodendrocytes in the CA1 of hippocampus was investigated with the immunohisto－chemical method and the stereological method. Results：After 7 weeks CUS intervention，the body weight of CUS group（251.4±15.9） g was significantly decreased when compared with that of control group（323.3±25.9） g（P=0.000），but the body weight of CUS group was not significantly different from the body weight of FLX group（257.9±22.7） g（P=0.473）. The sucrose preference of the CUS group（62.0±14.2）% was significantly lower than that of the control group（89.2±4.8）%（P=0.000） and FLX group（78.2±12.8）%（P=0.020）. The stereological results showed that CNPase+ cells in the CA1 field of the hippocampus in CUS group（18 650.7±1 812.0） was significantly decreased compared with that in control group（33 606.9±4 471.4）（P=0.007） and that in FLX group（29 080.7±2 877.5）（P=0.042）. Conclusion：The number of CNPase+ oligodendrocytes in the CA1 of hippocampus of the CUS rats is significantly decreased. Fluoxetine might prevent the loss of CNPase+ oligodendrocytes in the CA1 of hippocampus of the depression rats induced by CUS. The oligodendrocytes in the CA1 of hippocampus play an important role in the pathogenesis of depression. The current result might provide structural basis for the future studies that search for the new antidepressant strategies.