一种新型肝郁化火型抑郁症动物模型的建立及评价方法  

Establishment and evaluation methods of a novel animal model of liver depression transforming into fire syndrome-related depression

作　　者：苏丹[1] 李健 朱根华[1] 杨明[1,3] 廖亮亮 艾志福 李惠珍[1,2] 刘亚丽 宋永贵[1,2] SU Dan;LI Jian;ZHU Gen-hua;YANG Ming;LIAO Liang-liang;AI Zhi-fu;LI Hui-zhen;LIU Ya-li;SONG Yong-gui(Key Research Laboratory for Chinese Medicine Efficacy Evaluation(Prevention and Treatment of Mental Disorders Brain Disease)of Jiangxi Traditional Chinese Medicine Administration/Key Research Laboratory for Depression Syndrome Animal Models of Jiangxi Traditional Chinese Medicine Administration,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Key Laboratory of Pathological Research on Experimental Animals,Nanchang,Jiangxi University of Chinese Medicine,Nanchang 330006,China;Jiangxi Guxiang Jinyun Comprehensive Health Industry Co.,Ltd.,Nanchang 330029,China;Key Laboratory of Pharmacodynamics and Safety Evaluation,Health Commission of Jiangxi Province,Nanchang Medicine College,Nanchang 330004,China)

机构地区：[1]江西中医药大学,中药药效(防治精神障碍脑疾病)评价江西省中医药管理局重点研究室/抑郁症中医证候动物模型江西省中医药管理局重点研究室,江西南昌330004 [2]江西中医药大学,南昌市实验动物病理研究重点实验室,江西南昌330006 [3]江西古香今韵大健康产业有限公司,江西南昌330029 [4]南昌医学院,药效与安全性评价江西省卫生健康重点实验室,江西南昌330004

出　　处：《药学学报》2024年第6期1680-1690,共11页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(82260764,82074014);江西省教育厅科技计划项目(GJJ218915,GJJ2200901);江西省中医药科技计划(2021Z011);江西省科技计划(20232ACB206056,20224ACB218008).

摘　　要：通过一种复合诱导方法,结合神经行为学、宏观表征以及客观病理评价指标,构建并确证小鼠肝郁化火证抑郁模型。采用睡眠剥夺结合光照和隔天给粮刺激的方法进行构建,并从表观效度、结构效度和预测效度3个层次展开评估,再经由方剂反证所建立的肝郁化火型抑郁模型。表观效度中,与空白组相比,模型小鼠神经行为学表现为典型的抑郁样症状;一般状态观察显示模型组小鼠毛发乱而无光泽,且反应迟钝易激惹,饮水量大幅增加;小鼠睡眠时相检测中,模型小鼠睡眠觉醒期所占时间比显著上升,非快速眼动睡眠期和快速眼动睡眠期所占时间比显著下降;颈内动脉平均血流速度、血流量、舌、尿液、爪色r值等生理性指标变化有显著性差异;结构效度显示,与空白组相比,模型小鼠海马中五羟色胺、多巴胺、γ-氨基丁酸显著下降,乙酰胆碱、色氨酸、谷氨酸水平显著上升,给予丹栀逍遥散治疗后,以上神经递质皆有不同程度回调。预测效度中,治疗药物帕罗西汀可有效改善模型小鼠的抑郁样行为;肝郁化火经典方丹栀逍遥散可不同程度回调抑郁及相关证候各项指标。本研究建立了一种新型肝郁化火型抑郁动物模型,扩充了中医证候抑郁模型的种类,为今后中医药防治抑郁症的科学内涵研究、药效评价以及药物筛选提供了更多选择。动物实验获得江西中医药大学动物伦理实验委员会的批准和监督(伦理编号:20230313040)。Through a compound induction method,combined with neurobehavioral,macroscopic characterization and objective pathological evaluation indicators,a murine depression model of liver depression transforming into fire syndrome was constructed and confirmed.The model was constructed using a combination of sleep deprivation,light exposure,and alternate-day food deprivation.Evaluation was conducted at three levels:face validity,constructs validity,and predictive validity.The establishment of the liver depression transforming into fire syndrome depression model was further validated through the counterproof of traditional Chinese medicine formulas.In terms of face validity,compared to the control group,mice in the model group exhibited typical depressive symptoms in neurobehavioral assessments;the general observation of the model group mice reveals disheveled and lackluster fur,along with delayed and easily agitated responses.Additionally,there is a substantial increase in water consumption.In the sleep phase detection of mouse,the model group showed a significant increase in the proportion of time spent in the wake phase during sleep,accompanied by a significant decrease in the proportions of time spent in both non-rapid eye movement(NREM)and rapid eye movement(REM)sleep phases.There are significant differences in physiological indicators such as average blood flow velocity,blood flow rate,tongue,urine,and claw color(r values)in the internal carotid artery.Structural validity demonstrated that levels of 5-hydroxytryptamine(5-HT),dopamine(DA),andγ-aminobutyric acid(GABA)in the hippocampus of model mice decreased significantly,while acetylcholine(ACh),tryptophan(Try),and glutamic acid(Glu)levels increased significantly.Treatment with Danzhi Xiaoyao San led to varying degrees of restoration in the aforementioned neurotransmitters.In terms of predictive validity,the antidepressant paroxetine effectively ameliorated depressive behaviors in the model mice,and the classic formula Danzhi Xiaoyao San demonstrated varying degrees

关 键 词：抑郁症 动物模型 肝郁化火 丹栀逍遥散 病症结合 

分 类 号：R966[医药卫生—药理学]