实验动物与比较医学2024，Vol.44Issue(3)：259-269,11.DOI:10.12300/j.issn.1674-5817.2024.005
慢性不可预知性应激与完全弗氏佐剂、福尔马林诱导的妊娠期疼痛-抑郁共病小鼠模型的构建与评价
Establishment and Evaluation of Mouse Model of Pregnancy Pain-depression Comorbidity Induced by Chronic Unpredictable Stress,Complete Freund's Adjuvant and Formalin
摘要
Abstract
Objective To establish a mouse model of pregnancy pain-depression comorbidity induced by chronic unpredictable stress(CUS),complete Freund's adjuvant(CFA),and formalin,and to systematically evaluate the associated phenotypes and preliminarily explore the pathological basis of the comorbidity.Methods Eight-week-old C57BL/6J female mice were randomly strarified divided into a control group(no intervention before pregnancy)and a CUS model group(CUS intervention before pregnancy)based on sucrose preference test(SPT)data.After completing the CUS treatment,female and male mice were paired and mated.Pain was induced by injecting 50％CFA and 5％formalin in the right hind foot during pregnancy to create a model of pregnancy pain-depression comorbidity.The experiment was divided into 8 subgroups:control-blank group,CUS-blank group,control-CFA group,CUS-CFA group,control-formalin group,CUS-formalin group,control-CFA+formalin group,and CUS-CFA+formalin group,with 10 mice in each group.The mice in each group were subject to behavioral tests,including the SPT,forced swimming test,tail suspension test,and open field test before and after CUS intervention,during pregnancy,and after delivery.Pain sensitivity changes were measured using mechanical allodynia and thermal hyperalgesia tests.Mice were then euthanized.Levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in hippocampus,as well as cortisol and adrenocorticotropic hormone(ACTH)in serum,were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with the control-blank group,the CUS-blank group showed a significant depression-like behavior with reduced pain threshold(P＜0.001).The control-CFA+formalin group showed a decrease in pain threshold after both CFA injection and formalin injection(P＜0.01).Compared with the control-blank and control-formalin groups,the pain threshold was significantly lower in the CUS-formalin group(P＜0.01),with a sequential decrease among the three.Compared with the control-blank and control-CFA groups,the pain threshold was significantly lower in the CUS-CFA group(P＜0.001),with a sequential decrease among the three.Compared with the control-blank and control-CFA+formalin groups,the mechanical pain threshold of mice in the CUS-CFA+formalin group was significantly lower(P＜0.001)and the thermal radiation tolerance time was shorter(P＜0.01),both with sequential decreases among the three.Compared with the control-CFA+formalin and the CUS-blank groups,the CUS-CFA+formalin group had a significantly lower percentage of sucrose preference(P＜0.001),longer immobility time during the forced swimming test(P＜0.001)and tail suspension test(P＜0.001),reduced central exploration time in the open field test(P＜0.001),reduced total exploration distance(P＜0.001),and reduced percentage of distance traveled for central exploration(P＜0.001).Compared with the control-CFA+formalin and CUS-blank groups,the serum cortisol and ACTH levels of the CUS-CFA+formalin group were significantly higher(P＜0.01),and the levels of IL-6 and TNF-α in the hippocampus were higher(P＜0.05).Conclusion The combination of CUS+CFA+formalin injections is an ideal method for establishing a C57BL/6J mouse model of pregnancy pain-depression comorbidity.The behavioral changes in model mice may be attributed to the regulation of inflammatory response in hippocampus and hormone levels in the hypothalamic-pituitary-adrenal(HPA)axis.关键词
妊娠期抑郁/疼痛/共病/炎症因子/下丘脑-垂体-肾上腺轴/C57BL/6J小鼠Key words
Pregnancy depression/Pain/Comorbidity/Inflammatory factors/Hypothalamic-pituitary-adrenal axis/C57BL/6J mice分类
医药卫生引用本文复制引用
张一粟,刘欣茹,武若杰,刘睿,欧阳红,李晓红..慢性不可预知性应激与完全弗氏佐剂、福尔马林诱导的妊娠期疼痛-抑郁共病小鼠模型的构建与评价[J].实验动物与比较医学,2024,44(3):259-269,11.基金项目
蚌埠医科大学研究生科研创新计划项目"基于海马区BDNF表达和GSK-3磷酸化交互作用探讨艾司氯胺酮对小鼠围生期疼痛-抑郁共病的作用和机制"(Byycx22098) （Byycx22098）
