阿立哌唑对PTSD大鼠焦虑样行为及额叶皮质BDNF表达的影响

Effects of Aripiprazole on anxiety-like behavior and BDNF expression in prefrontal cortex of rat PTSD model

目的探讨腹腔注射阿立哌唑(ARP)对创伤后应激障碍(PTSD)大鼠焦虑样行为及额叶脑源性神经影响因子(BDNF)表达的影响。方法选取48只健康雄性SD大鼠,随机分为正常组(n=12)和模型组(n=36),模型组大鼠通过单程长时应激(SPS)建立PTSD大鼠模型,根据腹腔注射药物的不同将PTSD大鼠分为vehicle、ARP14d和ARP21d组;通过旷场实验和高架十字迷宫实验检测各组大鼠焦虑样行为;行为学检测后处死动物并取材,利用免疫荧光染色、Western blot和Real-time PCR检测各组大鼠额叶BDNF蛋白及mRNA表达。结果与vehicle组比较,ARP21d组大鼠在旷场中心停留的时间、旷场中心区域运动的距离、在高架十字迷宫开放臂停留时间及进入开放臂次数明显升高(P<0.05)。与对照组比较,vehicle组大鼠额叶BDNF表达水平显著降低(P<0.05),而ARP14d和ARP21d组大鼠额叶BDNF表达水平显著高于vehicle组(P<0.05)。结论腹腔注射阿立哌唑可以改善PTSD大鼠焦虑样行为,可能与额叶BDNF表达水平升高相关。

Objective To investigate the effects of aripiprazole（ARP） on anxiety like behavior and expression of brain derived neurotrophic factor （ BDNF ） in posttraumatic stress disorder（PTSD） rats. Methods 48 healthy male SD rats were randomly divided into control group（n=12）, vehicle group（n=12）, ARP14d group（n=12） and ARP21d group（n=12）. Open-field test, elevated plus-maze test were used to detect the anxiety behavior of rats. The expression of BDNF in prefrontal cortex of animals was detected by immunofluorescence staining, Western blot and Real-time PCR. Results Compared with vehicle group, the time in the center and the distance in the center of open field, and the percentage of open arm time, the percentage of open arm entries in elevated plus-maze were increased significantly in ARP21d group（P〈0.05）. The expression level of BDNF in prefrontal cortex was decreased in vehicle group than in control group, but increased in ARP14d and ARP21d group than in vehicle group（P〈0.05）. Conclusion Aripiprazole could ameliorate anxiety behavior of PTSD rats and this effect maybe related to the increased expression of BDNF in prefrontal cortex.