氟西汀对慢性应激大鼠海马磷酸化微管相关蛋白-2表达的影响

Effect of Fluoxetine on the Level of Phosphorylated Microtubule Associated Protein-2 in the Hippocampus of Chronically Stressed Rats

目的探讨慢性应激大鼠海马磷酸化微管相关蛋白-2(p-MAP-2)表达的变化及经典抗抑郁剂氟西汀的效应。方法24只SD大鼠,随机分为3组:正常对照组,慢性应激组,慢性应激伴随给予氟西汀(FLU,10mg·kg-1)组。慢性应激28d之后,用开场实验及新奇抑制摄食模型评价氟西汀的抗抑郁活性,用免疫组织化学方法及Western blot方法检测海马p-MAP-2的表达。结果慢性应激28d可以导致大鼠自发活动明显减弱,新奇抑制摄食潜伏期显著延长,慢性应激同时伴随给予氟西汀可以逆转这些行为学变化,提示氟西汀在慢性应激模型上具有良好的抗抑郁作用;免疫组化研究发现,与对照组比较,慢性应激可以导致大鼠海马p-MAP-2表达水平明显降低,而同时伴随给予氟西汀可以提高其表达水平;Westernblot结果进一步研究发现,慢性应激可以使大鼠海马p-MAP-2A以及低分子量p-MAP-2C表达明显降低,而同时伴随给予氟西汀可以逆转这些变化。结论海马p-MAP-2各亚型表达的变化与氟西汀在慢性应激模型上抗抑郁活性有关。

Aim To investigate changes of phosphorylated microtubule associated protein-2 phosphorylation （ p- MAP-2） in hippocampus of chronically stressed rats, and to explore effects of fluoxetine on them. Methods 24 male Sprague-Dawley rats were divided randomly into three groups： control group, chronic stress group and chronic stress ＋ fluoxetine （10mg.kg^-1 ） group. Then open field test and novelty suppressed feeding were used to verify the model we used. The level of p-MAP-2 was evaluated by immunohistochemistry and Western blot. Results The locomotor activity of the stressed rats in the open field was significantly decreased and the latency of the stressed rats to eat was increased, while chronic Co-administration with 10mg.kg^-1 fluoxetine could reverse these changes, indicating that fluoxetine had an antidepressant effect in the chronically stressed model of rats. Compared with the control, rats which received chronic stress showed significantly decreased immunostaining for the p-MAP-2 by the method of immunohistochemistry. Co-administration with fluoxetine could increase the level of p-MAP-2. The resuits of Western blot also indicated that chronic stress significantly diminished p-MAP-2, especially the level of the low molecular weight p-MAP-2C, while co-administration with fluoxetine could reverse this change. Conclusion These results suggested that alteration in hippocampal p-MAP-2 appeared to be highly correlated with behavioral effect of fluoxetine in chronically stressed rats.