Li Yuefeng, Yan Jinchuan, Zhu Xiaolan, Zhu Yan, Yao Shun, Xu Yuhao, Ju Shenghong
Department of Radiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
J Affect Disord. 2017 Sep;219:17-24. doi: 10.1016/j.jad.2017.04.035. Epub 2017 Apr 21.
The occurrences of dilated Virchow-Robin spaces (dVRSs) and inflammatory factors were closely related with development of depression and antidepressants. The present study indicated accumulation of inflammatory factors in dVRSs played a practical role in behaviors and the treatment-resistant in rats with depression. Eighty-one male Wistar rats were exposed to chronic unpredictable mild stress (CUMS) until the model was successfully established. According to the detection of dVRSs on 7 T structural magnetic resonance imaging (MRI), rats were divided into two groups (45 CUMS rats and 36 CUMS rats). Subsequently, different antidepressant treatment (nontreat, aspirin, fluoxetine, fluoxetine+aspirin) was given to the two groups, respectively. Sucrose preference test (SPT), forced swim test (FST) and morris water maze (MWM) was used to test the behaviors of rats. ELISA and Western blot was used to determine the levels of inflammatory factors. Compared with the negative control (NC) group, there were obvious behavioral abnormalities and increased inflammatory factors in the CUMS rats. Interestingly, these changes were more significant in the CUMS rats. In addition, the efficacy of fluoxetine was only found in CUMS rats rather than CUMS rats. Meanwhile, behaviors and levels of inflammatory factor in hippocampus were ameliorated in the aspirin group of CUMS rats, and these effects were significantly enhanced in the fluoxetine+aspirin group. The dVRSs in the hippocampus might exacerbate depression-like behaviors and the effects of antidepressant treatment in depressed rats by increasing the levels of inflammatory factors.
扩张型血管周围间隙（dVRSs）的出现与炎症因子和抑郁症的发展及抗抑郁药密切相关。本研究表明，dVRSs中炎症因子的积累在抑郁症大鼠的行为和难治性方面发挥了实际作用。81只雄性Wistar大鼠暴露于慢性不可预测轻度应激（CUMS）下，直至模型成功建立。根据7T结构磁共振成像（MRI）对dVRSs的检测，将大鼠分为两组（45只CUMS大鼠和36只CUMS大鼠）。随后，分别对两组给予不同的抗抑郁治疗（不治疗、阿司匹林、氟西汀、氟西汀+阿司匹林）。采用蔗糖偏好试验（SPT）、强迫游泳试验（FST）和莫里斯水迷宫（MWM）测试大鼠行为。采用ELISA和蛋白质免疫印迹法测定炎症因子水平。与阴性对照组（NC）相比，CUMS大鼠存在明显的行为异常且炎症因子增加。有趣的是，这些变化在CUMS大鼠中更为显著。此外，仅在CUMS大鼠而非CUMS大鼠中发现氟西汀的疗效。同时，CUMS大鼠阿司匹林组海马区的行为和炎症因子水平得到改善，在氟西汀+阿司匹林组中这些作用显著增强。海马区的dVRSs可能通过增加炎症因子水平加重抑郁大鼠的抑郁样行为及抗抑郁治疗效果。
