慢性脑低灌注大鼠焦虑样行为与海马区域炎性细胞因子水平的相关性分析

目的:分析慢性脑低灌注(CCH)大鼠模型焦虑样行为和海马和血清炎性细胞因子水平的相关性。方法:将成年雄性Sprague-Dawley(SD)大鼠(200-220 g)分为两组(假手术(sham)和双侧颈总动脉结扎(BCCAO)组,每组N=40),分别给予BCCAO或者假手术。造模4周后,通过旷场实验和高架十字迷宫测试大鼠焦虑样行为;间接免疫荧光(Iba1和GFAP染色)和酶联免疫吸附实验(ELISA)分别测定海马CA1区胶质细胞激活和血清及海马区域白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、细胞粘附分子-1(ICAM-1)和血管细胞粘附分子-1(VCAM-1))水平。结果:旷场实验结果表明相比sham组,BCCAO组总穿行距离、中央区穿行距离和停留时间明显增多(P<0.05),高架十字迷宫实验中BCCAO组开臂停留时间和访问次数明显增加(P<0.05),闭臂停留时间显著缩短(P<0.05)。另外,相比sham组,BCCAO组大鼠海马CA1区胶质细胞明显激活,海马以及血清中炎性因子的表达水平均显著上调。Pearson相关性分析显示海马区域而非血清ICAM-1和VCAM-1水平与CCH大鼠焦虑样行为(中央区和开臂的停留时间)呈显著正相关(P<0.05)。结论:海马区域ICAM-1和VCAM-1升高与CCH大鼠焦虑样行为显著相关,可能参与CCH慢性期焦虑样行为的发生。

Correlative Analysis between the Anxiety-like Behaviors and Hippocampal Inflammatory Cytokine Levels in a Rat Model of Chronic Cerebral Hypoperfusion

Objective: To analyze thel correlation between anxiety-like behavior and hippocampus/serum inflammatory reactive substances in chronic cerebral hypoperfusion(CCH) in rats. Methods: Adult male Sprague-Dawley(SD) rats(200-220 g) were divided into two groups(sham and bilateral common carotid artery ligation(BCCAO) groups, N=56 per group) and underwent BCCAO or sham surgery, and. After 4 weeks, the open field test and the elevated plus maze were used to test rats’ anxiety-like behavior;immunofluorescence(Iba1 and GFAP staining) and enzyme-linked immunosorbent assay(ELISA) were used to determine glial activation in the hippocampal CA1 region and serum and hippocampus interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), cell adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) content respectively. Results: Open field test showed that the total walking distance of the BCCAO group was significantly higher than that of the sham group, as well as the walking distance and time spent in the central zone(P<0.05). In the elevated plus maze, the BCCAO group revealed significantly increased time spent in the open arm and number of visits, while the closed arm stay time was significant lower(P<0.05). In BCCAO group glial cells was significantly activated compared with sham group in hippocampal CA1, and the expression levels of inflammatory factors in both of the hippocampus and serum in BCCAO group were detected(P<0.05). Correlative analysis indicated that expression levels of ICAM-1 and VCAM-1 in hippocampus(rather than serum) were positively associated with anxiety-like behavior(time spent in the center and open arm)(P<0.05). Conclusion:ICAM-1 and VCAM-1 in the hippocampus participate in the pathological process of chronic anxiety-like behavior in the CCH model.