抽动障碍肝阳上亢证病证结合大鼠模型的对比研究  

Comparative study on rat models of tourette disorder with hyperactivity of liver Yang syndrome combined with disease and syndrome

作　　者：张心放 吴振起 赵雪[3] 郝欧美[3] 王子 ZHANG Xinfang;WU Zhenqi;ZHAO Xue;HAO Oumei;WANG Zi(Graduate School of Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学研究生学院,沈阳110847 [2]辽宁中医药大学附属第二医院儿科 [3]辽宁中医药大学附属医院儿科

出　　处：《环球中医药》2024年第6期1043-1049,共7页Global Traditional Chinese Medicine

基　　金：沈阳市科技计划项目(21-174-9-01)。

摘　　要：目的构建亚氨基二丙腈(iminodiProPion-itri,IDPN)、2,5-二甲氧-4-碘苯-2-氨基丙烷(5-dimethoxy-4-uodoPhenyl-2-aminoProPan,DOI)、阿扑吗啡(aPomorPhine,APO)3种抽动障碍(tic disorder,TD)大鼠模型对其行为特征、激惹状态及相关递质变化进行比较;选择表观效度及结构效度良好的TD模型分别加载不同应激刺激,构建、评价及筛选最优TD肝阳上亢证病证结合大鼠模型。方法120只SD大鼠随机分为6组:对照组正常饲喂,不做特殊处理;IDPN组腹腔注射IDPN溶液持续1周;DOI组、APO组分别腹腔注射DOI溶液、APO溶液持续2周;APO复合束缚悬吊应激(restraint and suspension stress,RSS)模型组(APO+RSS组)腹腔注射APO溶液2周同时复合慢性束缚悬吊应激持续3周;APO复合声电刺激应激(acoustic and electrical stimulation stress,AESS)模型组(APO+AESS组)腹腔注射APO溶液2周同时复合声电刺激应激持续3周。通过行为学实验评估大鼠刻板运动、自发活动及情绪障碍;酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)法测定纹状体中多巴胺(dopamine,DA)、γ-氨基丁酸(γ-aminobutyric acid,GABA)、谷氨酸(glutamate,GLU)、五羟色胺(serotonin,5-HT)水平变化,血清中血管紧张素II(Angiotensin II,AngⅡ)、精氨酸加压素(arginine vasopressin,AVP)水平变化。结果APO、DOI、IDPN诱导造模结果显示,与对照组比较,3种造模方式均可成功诱导大鼠的自发活动、刻板运动、认知及情绪障碍。IDPN组表现为更明显的刻板运动、认知障碍及焦虑抑郁倾向,与对照组相比DA、GLU水平降低(P<0.05),5-HT水平升高(P<0.05);APO组表现为更明显的自发活动及兴奋、易激惹状态、探索及攻击行为增多,与对照组相比DA、GLU水平升高(P<0.05),AngⅡ水平显著升高(P<0.01);DOI组大鼠行为学表现与APO组相似,但自发活动、刻板运动程度较APO组差;与对照组相比DOI组5-HT水平显著降低(P<0.01)。APO加载复合模型比较结果显示,APO+RSS组大�Objective Three rat TD models,IDPN,DOI and APO,were constructed to compare their behavior characteristics of simulated TD,and changes in relevant transmitters;TD models with good apparent andcharacteristics of hyperactivity of liver yang were selected to load different stress stimuli separately to build composite models,to evaluate and screen the optimal TD hyperactivity of liver yang rat model with integration of disease and syndrome.Methods 120 male Sprague-Dawley rats were randomly divided into six groups:rats in the control group were fed without special treatment;the IDPN group was intraperitoneally injected with IDPN solution for a week;the DOI group and the APO group were intraperitoneally injected with DOI solution and APO solution respectively for 2 weeks;the APO+RSS group was intraperitoneally injected with APO solution for 2 weeks and combined restraint and suspension stress for 3 weeks;the APO+AESS group was intraperitoneally injected with APO solution for 2 weeks and combined acoustic electrical stimulation stress for 3 weeks.Behavioral tests were used to evaluate the stereotypical movements,spontaneous activity and emotional disorders in rats;the method of ELISA was used to determine the levels of DA,GABA,GLU and 5-HT in the striatum and the levels of Ang II and AVP levels in the serum.Results APO,DOI,IDPN induction moulding results show that compared with the control group,the three modeling methods could successfully induce spontaneous activity,stereotypical movements,cognitive and emotional disorders in rats.The IDPN group showed more pronounced stereotyped movements,cognitive impairment and a tendency to anxiety and depression,with reduced levels of DA and GLU and increased levels of 5-HT compared with the control group(P<0.05);the APO group showed more pronounced spontaneous activity and increased excitement,irritability,exploratory and even aggressive behaviour,with increased levels of DA and GLU(P<0.05)and significantly higher levels of Ang II compared to the control group(P<0.01);the behavio

关 键 词：抽动障碍 肝阳上亢证 应激 模型 大鼠 

分 类 号：R285.5[医药卫生—中药学]