摘要
【目的】建立基于化学遗传的慢性应激导致抑郁症的小鼠模型,为优化慢性应激诱发抑郁症的动物建模方法提供参考。【方法】通过化学遗传的方法,对小鼠延髓腹外侧区头端(RVLM)进行持续的刺激,模拟机体对慢性应激的响应,系统观察造模和对照组小鼠的行为学、血压及主要炎症因子的变化情况。【结果】成功建立了小鼠模型。经腹腔向小鼠给药CNO 1 h后,造模组较对照组的舒张压与平均脉压显著上升。持续给药4周后,造模组较对照组的旷场实验的水平运动总距离、中央区进入总次数、中央区滞留时间和中央区域运动总距离这四项指标均显著下降;蔗糖偏好实验提示造模组存在快感缺失;转棒实验提示造模组运动协调能力显著减弱;同时,造模组心率、血压、炎性因子IFN-γ和抑炎因子IL-10水平等也较对照组显著上调。【结论】我们的模型在诱发抑郁症经典症状,及血压偏高、炎性因子释放紊乱等抑郁症伴随症状上均表现出较高的成功率和稳定性。这为优化慢性应激诱发抑郁症的动物建模效率和稳定性提供了有参考价值的科学依据。
【Objective】To establish a chronic stress inducing depressive disorder mouse model via chemical genetics,that helps to optimize the animal modeling method of chronic stress-induced depressive disorder.【Methods】To continuously stimulate the rostral ventrolateral medulla(RVLM)of mouse by chemical genetic method to mimic the response to chronic stress.The changes about behavior,blood pressure and major inflammatory factors of the animal models were correspondingly observed.【Results】The mouse model was established successfully.One hour after intraperitoneal administration of CNO,diastolic blood pressure and mean blood pressure were significantly increased in the model group compared with the control.After four weeks of continuous administration,the total distance of movement,the total entering bouts,the distance and duration of the central area in the model group were significantly decreased compared with the control in the open field experiment.The results of sucrose preference and rotarod experiment suggested anhedonia and weakened motor coordination ability in the model group.The heart rate,blood pressure,expressions of IFN-γand IL-10 in the model group were higher than those in the control.【Conclusions】Our model developed classic symptoms of depressive disorder efficiently and stably,as well as accompanying symptoms such as high blood pressure and mussy release of inflammatory factors.It provides a valuable scientific basis for improving the efficiency and stability of animal modeling of chronic stressinduced depressive disorder.
作者
邓艺雯
张寅航
徐兴浩
蚁焌哲
张小然
黄玮俊
DENG Yi-wen;ZHANG Yin-hang;XU Xing-hao;YI Jun-zhe;ZHANG Xiao-ran;HUANG Wei-jun(Center for Stem Cell Biology and Tissue Engineering,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou 510080,China)
出处
《中山大学学报（医学科学版）》
CAS
CSCD
北大核心
2021年第3期346-354,共9页
Journal of Sun Yat-Sen University:Medical Sciences
基金
国家自然科学基金(81970222)
广东省科技计划项目(2016B090918040,2017B020230004)。
