不同抑郁症模型下证候差异的品系依赖性研究

An Empirical Study on Strain-Dependent Phenotypes of Traditional Chinese Medicine Syndrome of Depression

目的:疾病与证候关系的本质是中医学研究的基本问题之一。本研究基于遗传(先天禀赋)参与决定疾病证候的原理,研究小鼠品系差异对抑郁症证候的影响。方法:使用皮质酮皮下重复注射及慢性温和不可预知应激两种方式,在Balb/c和129/S1两种近交系小鼠上进行抑郁症疾病造模。对模型动物进行糖水偏好实验、悬尾实验、强迫游泳实验、新奇环境摄食抑制实验、旷场实验等行为学检测,以及对小鼠证候表型特征:皮毛状态、掌纹血色度、抓力和负重游泳实验进行检测。结果:雄性Balb/c小鼠在两种模型中分别表现出阈下抑郁样行为和抑郁样行为,但是在抓力及掌纹血色表型上都显示气虚样证候。雄性129/S1小鼠在两种模型下都表现出抑郁样行为,从行为绝望分析表现为气郁样证候。两个品系在两种模型下皮毛评分都增加,提示此表型与气虚与气郁都有关系。结论:本研究显示抑郁症证候呈现品系依赖性,且一定程度上独立于造模方法。这为我们进一步利用如全基因组关联分析等现代技术研究病证相关性的现代生物学本质奠定了基础。

The essence of the relationship between disease and traditional Chinese medicine（TCM） syndrome is one of the basic problems in the research of TCM.Based on the principle of genetic（innate endowment）involvement in determining disease-syndrome,this study aimed to analyze the effects of different mouse strains on the TCM syndrome of depression.Repeated injections of corticosterone and chronic unpredictable mild stress（CUMS） were used for modeling depression in two inbred strain mice,Balb/c and 129/Sl.Animals were tested for sucrose preference,tail suspension,forced swimming,novelty suppressed feeding,open filed activities,as well as fur condition,degree of redness in the palm,grasping force,and loaded swimming tests for TCM syndrome phenotypes.The results showed that male Balb/c strain mice exhibited subthreshold depressive-like behavior and depressive-like behavior respectively in two models.However,grasping force and degree of redness in the palm in both models indicated qi deficiency syndrome.Male 129/Sl mice showed depressive-like behavior in both models.Meanwhile,the behavior despair indicated the qi stagnation syndrome in both models.In both strains and both models,the fur condition was worsen,suggesting the phenotype was associated with both syndromes.It was concluded that TCM syndrome of depression was strain-dependent,and to some extent,independent of the disease model.This study lays a foundation for further utilization of modern technologies such as genome-wide association study to investigate the relationship between disease and TCM syndrome.