创伤后应激障碍小鼠海马组织炎性因子水平与行为学的关系

Relationship between levels of inflammatory factors and behavior in hippocampus of rats with posttraumatic stress disorder

目的:探讨创伤后应激障碍小鼠血清炎性因子与认知能力的关系。方法:将50只小鼠按照随机数字表法分为对照组和实验组,实验组小鼠采用巴甫洛夫条件性恐惧建立创伤后应激障碍(PTSD)模型,采用酶联免疫吸附试验(ELISA)分析海马组织中肿瘤坏死因子-α(TNF-α)和白细胞介素(IL)-6表达水平,采用旷场实验、高架十字迷宫实验和水迷宫实验检测小鼠行为学变化。采用相关性分析海马组织炎性因子TNF-α和IL-6表达水平与行为学指标的关系。组间比较采用t检验。结果:对照组小鼠海马组织中炎性因子TNF-α和IL-6表达水平[(1.39±0.15)、(3.77±0.20)pg/ml]明显低于实验组海马组织[(7.01±0.53)、(10.49±1.43)pg/ml],差异有统计学意义(t=4.129、4.918,P<0.05)。旷场实验结果显示,对照组小鼠运动总路程和中央格停留时间分别为(312.41±22.90)m、(16.33±6.19)s明显高于实验组(263.19±15.37)m、(6.98±2.47)s,差异有统计学意义(t=6.992,P<0.05;t=5.109,P<0.05)。高架十字迷宫实验结果显示,对照组小鼠开环时间比例[(37.21±8.12)%]明显高于实验组小鼠[(18.48±6.29)%],而对照组小鼠闭环时间比例[(62.79±9.14)%]明显低于实验组小鼠[(81.52±7.98)%],差异均有统计学意义(t=4.104,P<0.05;t=3.894,P<0.05)。水迷宫实验结果显示,对照组小鼠目标象限停留时间[(25.28±7.09)s]明显高于实验组[(16.32±6.01)s],差异有统计学意义(t=4.273,P<0.05)。PTSD小鼠海马组织炎性因子TNF-α和IL-6水平与闭环时间比例呈正相关(r=0.385、0.297,P<0.05),而与运动总路程、中央格停留时间、开环时间比例和目标象限停留时间等指标呈负相关(r=-0.269、-4.590、-0.418、-0.501、-0.381、-4.023、-0.463、-0.428,P<0.05)。结论:PTSD小鼠海马组织炎症因子TNF-α和IL-6水平和焦虑程度明显增加,而自主运动能力和学习能力明显下降。

Objective To investigate the relationship between serum inflammatory factors and cognitive ability in mice with post-traumatic stress disorder(PTSD).Methods Totally,50 mice were randomly divided into control group and experimental group by random number table method.The PTSD model was established by Pavlov′s conditioned fear in experimental group.The levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in hippocampus were analyzed by enzyme linked immunosorbent assay(ELISA).Open field test,elevated cross maze test and water maze test were used to detect the behavioral changes.The relationship between the expression levels of TNF-αand IL-6 in hippocampus and behavioral indexes was analyzed by correlation analysis.T test was used for comparison between groups.Results The expression levels of TNF-αand IL-6 in the hippocampus of the control group[(1.39±0.15)and(3.77±0.20)pg/ml respectively]were significantly lower than those in the experimental group[(7.01±0.53)and(10.49±1.43)pg/ml,t=4.129,4.918,P<0.05].The open field experiment showed that the total distance and central grid residence time in the control group were(312.41±22.90)m and(16.33±6.19)s,which were significantly in increased as compared with those in experimental group[(263.19±15.37)m and(6.98±2.47)s,respectively(t=6.992,5.109,P<0.05).Elevated cross maze test showed that the proportion of open-loop time in the control group[(37.21±8.12)%]was significantly longer than that in the experimental group[(18.48±6.29)%],and the proportion of closed-loop time in the control group[(62.79±9.14)%]was significantly shorter than that in the experimental group[(81.52±7.98)%,t=4.104,3.894,P<0.05].Water maze test showed that the residence time in the target quadrant of the control group[(25.28±7.09)s]was significantly longer than that in the experimental group[(16.32±6.01)s,t=4.273,P<0.05].The levels of TNF-αand IL-6 in the hippocampus of PTSD mice were positively correlated with the proportion of closed-loop time(r=0.385,0.297,P<0.05),but negatively correlated with the total distance of exercise,the central grid residence time,the proportion of open-loop time and the target quadrant residence time(r=-0.269,-4.590,-0.418,-0.501,P<0.05;r=-0.381,-0.297,-4.023,-0.463,-0.428,P<0.05).Conclusion The levels of TNF-αand IL-6 in hippocampus and the degree of anxiety in PTSD mice are significantly increased,while the ability of autonomous movement and learning are significantly decreased.