食蟹猴创伤后应激障碍动物模型的建立及行为和神经生物学变化

Establishment of animal model of post-traumatic stress disorder in cynomolgus monkeys and behavioral and neurobiological changes

目的:建立食蟹猴创伤后应激障碍(PTSD)动物模型的评价方法,探讨PTSD食蟹猴的皮质醇、多巴胺、脑源性神经营养因子、5-羟色胺等神经生理学指标在食蟹猴PTSD动物模型差异。方法:选取成年雌性食蟹猴60只,按照随机数字表法分为对照组(n=30)和实验组(n=30)。实验组食蟹猴,采用幽闭+电刺激制作食蟹猴PTSD实验动物模型,两组拘禁笼中拘禁100天,单笼喂养,同居一室。定时观察并记录两组动物行为学指标,期间并注意有无外伤、疾病发生。分别在拘禁前、半个月、1个月、3个月采集静脉血,检测两组神经生理学指标。所有观察数据统计分析前进行正态分布性检验,如果为正态分布,使用独立样本t检验,或多样本方差分析,如果显示数据为非正态分布,采用非参数Wilcoxon秩和检验,进行统计分析,显著性水平为α=0.05。结果:与对照组相比,实验组食蟹猴活动、好奇和恐惧行为、应激行为持续时间和次数显著差异(P<0.05);实验组食蟹猴血浆中肾上腺皮质激素和皮质醇的水平与对照组相比是上升的,差异存在显著性(t=0.345,7.137,4.529,4.180;P<0.05)。实验组食蟹猴BDNF及5-HT含量降低,与对照组相比显著差异(P<0.05);实验组TNF-α含量逐渐升高,与对照组相比同样有显著差异(P<0.05)。结论:实验食蟹猴易出现心理压力产生持久的PTSD样生理和行为异常与其机体'创伤性'暴露和缺乏社会支持有关;肾上腺皮质激素、皮质醇和BDNF、5-HT、NF-α水平的变化与失调的下丘脑-垂体-肾上腺(HPA)轴的应激影响有关。

Objective:To establish an evaluation method for PTSD animal models of cynomolgus monkeys,and explore the differences in neurophysiological indexes of PTSD cynomolgus monkeys such as cortisol,dopamine,brain-derived neurotrophic factor and serotonin in cynomolgus monkey PTSD.Methods:Sixty adult female cynomolgus monkeys were selected and divided into control group(n=30)and experimental group(n=30)according to the random number table method.In the experimental group,the cynomolgus monkey PTSD experimental animal model was designed by claustrophobia+electrical stimulation.The two groups were detained in cage for 100 days,single cage feeding and cohabitation.Regularly observed and recorded the behavioral indicators of the two groups of animals,and payed attention to whether there was any trauma or disease.Venous blood was collected prior to detention,half month,one month,and three months of detention,and the two groups’neurophysiological indicators were detected.All observations were tested for normal distribution before statistical analysis.If they were normal distribution,using independent sample t test or multi-sample ANOVA for statistical analysis.If the data was non-normally distributed,using nonparametric Wilcoxon rank sum test.Statistical analysis was performed with a significance level ofα=0.05.Results:Compared with the control group,the activity,curiosity and fear behavior,duration of stress behavior and frequency of cynomolgus monkeys in the experimental group were significantly different(P<0.05).The levels of corticosteroids and cortisol in the plasma of the experimental group were compared with the control group and the difference was significant(P<0.05).The levels of BDNF and 5-HT in the experimental group were significantly lower than those in the control group(P<0.05).The TNF-αcontent in the experimental group gradually increased,which was also significantly different from the control group(P<0.05).Conclusion:Experimental cynomolgus monkeys are prone to psychological stress,resulting in persistent PTSD-like physiological and behavioral abnormalities,which are related to'traumatic'exposure and lack of social support;adrenal cortex hormones,cortisol and BDNF,5-HT,NF-αlevels The changes are related to the stress effects of the hypothalamic-pituitary-adrenal(HPA)axis.