成纤维细胞生长因子2对创伤后应激障碍模型大鼠行为及海马星形胶质细胞的影响

Impact of fibroblast growth factor 2 administration on behavior and hippocampal astrocytes in rats with posttraumatic stress disorders

摘要:

目的 探讨成纤维细胞生长因子2（FGF2）对创伤后应激障碍（PTSD）模型大鼠的行为以及海马星形胶质细胞的作用。方法 采用单次延长应激（SPS）建立大鼠PTSD模型，然后在SPS大鼠第7d给予高剂量FGF2因子腹腔注射，采用自发活动、高架十字迷宫方法观察高剂量FGF2单次给药对SPS模型大鼠行为学的影响；同时利用星形胶质细胞标志物——胶质纤维酸性蛋白（GFAP）免疫荧光染色方法，观察各组大鼠海马星形胶质细胞阳性表达的情况，并利用双重荧光Western印迹法验证GFAP在不同实验组的蛋白表达情况。结果 与SPS组大鼠相比，FGF2高剂量给药后明显减轻SPS大鼠的焦虑或抑郁状态，且明显增强海马内GFAP免疫反应阳性星形胶质细胞的表达。结论 FGF2可明显改善SPS大鼠的焦虑或抑郁症状，其治疗PTSD的机制可能与增加星形胶质细胞的活性有关。

Abstract:

Objective To determine the effect of fibroblast growth factor 2 (FGF2) injection on the behavior and astrocytes activation in the hippocampus in the rats of posttraumatic stress disorders (PTSD). Methods Single prolonged stress (SPS) was used to establish the PTSD rat model. Then a single high dose of FGF2 (50μg/kg) was given by intraperitoneal injection in 7d after the model establishment. Another 7d later, open-field test (OF) and elevated plus maze (EPM) test were used to evaluate rats’ spontaneous activity, anxiety and depression behaviors. Immunofluorescence staining and double immunofluorescence Western blotting were used to detect the expression of glial fibrillary acidic protein (GFAP) in the hippocampus in normal, PTSD, and FGF2 treated rats for astrocytes activation and expression level respectively. Results FGF2 treatment resulted in significantly decreased anxiety and depression behaviors compared with the PTSD rats, and enhanced the expression of GFAP obviously in the hippocampus. Conclusion FGF2 obviously attenuates anxiety and depression behaviors in the rats after SPS, which might be due to its enhancement in astrocyte activity in the hippocampus.