【作者】 王志斌；

【导师】 李军祥；

【作者基本信息】 北京中医药大学 ， 中医内科学， 2014， 博士

【摘要】 本论文通过临床与实验研究阐述了现代医学及中医药对酒精依赖症的认识,以统计学作为研究工具探讨了酒精依赖症的中医证候学特点,并深入研究了和解泄热安神法对酒精依赖症患者生存质量的影响和该法对酒精依赖大鼠行为学及神经递质影响的作用机制,为今后阐明中医药治疗酒精依赖症的作用机理和中药开发提供依据。1酒精依赖症的中医证候特点研究目的对酒精依赖症患者的临床资料进行横断面调查,了解酒精依赖症患者证候学规律特点。方法本研究通过观察211例符合酒精依赖症诊断的门诊及住院患者。收集患者的一般症状信息、饮酒量,中医证候量表以及肝功能等信息。将上述信息数字化后,通过因子分析法及复杂系统熵聚堆分析法进行分析研究。结果通过因子分析和复杂系统熵聚堆对酒精依赖症的中医证候分类分析后,得出以下6个证型：肝肾阴虚,湿热气滞证(37例,17.5%)；肝阳上亢,阴虚内热证(19例,9.0%)；脾虚肝郁,湿热瘀阻证(66例,31.3%)；脾虚湿困证(18例,8.5%)；肝郁气滞,阴虚血瘀证(49例,23.2%)；湿热内盛证(22例,10.4%)。2和解泄热安神法对酒精依赖症患者生存质量的影响目的采用随机对照研究法观察和解泄热安神法对酒精依赖症患者生存质量的影响。方法将56名酒精依赖症患者随机分为两组,分别服用和解泄热安神法方药及安慰剂4周。并以健康状况问卷(Short Form36Health Survey Questionnaire, SF-36)为主要研究工具,量化评估和解泄热安神法方药对酒精依赖症患者生活质量的影响。结果经治疗前后SF-36计分数据比较,治疗组在服药4周后,在生理机能、生理职能、躯体疼痛、一般健康状况、精力、精神健康6个维度上的得分均高于对照组(p<0.05),社会功能、情感职能2个维度不具有统计学上的差异。同时治疗组在中医证候治愈率和显效率方面明显优于对照组,而组间比较具有明显统计学差异(P<0.05)。患者在胁肋胀满,倦怠乏力,食欲不振,情志抑郁,便秘及口苦6个证候指标治疗组的积分改善明显,与对照组比较具有显著的统计学差异(P<0.05)。3和解泄热安神法对酒精依赖症大鼠戒断行为及伏核多巴胺含量影响的研究实验一和解泄热安神法对酒精依赖症大鼠戒断行为影响的研究目的研究和解泄热安神法对酒精依赖症模型大鼠戒酒后戒断行为学评分的影响。方法通过连续自由饮含低浓度酒精饮水建立酒精依赖症动物模型。设立治疗组、对照组和正常组,并在实验进行3周后,治疗组大鼠应用解泄热安神法方药灌胃,对照组应用纯净水假灌胃,正常组则不进行干预。造模大鼠在实验的4周后撤除酒精饮水,给予纯净水。观察大鼠撤除酒精后不同时间(2h,6h,24h,48h)给予行为体征和听源性癫痫发评分。结果对照组大鼠在戒酒后的戒断症状评分在戒断后2、6、24h时均显著高于正常组大鼠(p<0.05)。而治疗组大鼠的行为则介于二者之间。48小时后各组的戒断行为学评分与正常组比较差异无显著性(P>0.05)。实验二和解泄热安神法对酒精依赖症大鼠伏核多巴胺含量影响的研究目的通过HPLC-MS/MS法研究和解泄热安神法对酒精依赖症模型大鼠戒酒后大脑伏核多巴胺含量的影响。方法造模及施药方案同实验一。通过HPLC-MS/MS法研究对比治疗组(高剂量、低剂量)、对照组在戒酒后大脑伏核多巴胺含量的差异。结果经HPLC-MS/MS法测定各组伏核多巴胺含量,分析发现,四组数据中对照组伏核内多巴胺含量最高2.14+0.32μ g/g,正常组最低0.96±0.38μ g/g,高剂量治疗组和低剂量治疗组分别为：1.43±0.41μg/g,1.50±0.28μg/g。两治疗组间数据无明显差异(p>0.05)；而上述两组与对照组对比有显著性差异(p<0.05)。更多还原

【Abstract】 This study aimed to explore TCM syndrome characteristics of Alcohol Dependence Syndrome (ADS) and effects of Harmonizing, Heat-discharging and Tranquillizing (HHdT) formula on quality of life (QOL) of ADS patients, and investigate therapeutic mechanisms of HHdT formula in terms of behavioral changes and neurohumoral transmission in ADS rats. Through the study, we hope to further understand therapeutic mechanisms of HHdT formula and therefore lay foundation for relevant Chinese drug development.1TCM syndrome characteristics of ADSObjectiveTo get a clear picture on TCM syndrome characteristics of ADS through the cross-sectional study.Methods211patients diagnosed as ADS were recruited in the study. The data involving the general information, alcohol consumption, assessment of individual symptoms, assessment of TCM syndrome and liver function were collected and statistically analyzed by factor analysis and complex system entropy cluster.ResultsADS involves6TCM syndrome types which include liver-kidney yin deficiency, dampness-heat and qi stagnation (37cases,17.5%), ascendant hyperactivity of liver-yang, yin deficiency with internal heat (19,9.0%), spleen deficiency and liver depression, dampness-heat and blood stasis (obstruction)(66,31.3%), spleen deficiency with dampness accumulation (18,8.5%); liver depression and qi stagnation, yin deficiency and blood stasis (49,23.2%), and internal dampness-heat (22,10.4%).2Effects of HHdT formula on QOL of ADS patientsObjectiveTo investigate effects of HHdT formula on QOL of ADS patients by the randomized controlled trial.Methods56alcohol-dependent patients were randomly divided into group A and group B. Group A were given HHdT herbal granules, while group B the placebo for4weeks. QOL of both groups was assessed after the treatment with Short Form36Health Survey Questionnaire (SF-36).ResultsAssessed by SF-36, the scores in terms of Physical Functioning (PF), Role Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Mental Health (MH) in group A were significantly higher than those in group B (P<0.05) while there was no significant difference in terms of Social Functioning (SF) and Role Emotional (RE) between the2groups.Assessed by the scales of particular ADS-related symptoms, the clinical control rate and the total relief rate in group A were significantly higher than those in group B (P<0.05). Compared with group B, the symptoms of group A in terms of distention and fullness in the hypochondrium, fatigue, poor appetite, depression, constipation and bitter taste in mouth were significantly relieved (P<0.05)3Effects of HHdT formula on behavioral changes and dopamine in nucleus accumbens (NAc DA) subsequent to alcohol withdrawal in ratsExperiment1Effects of HHdT formula on behavioral changes subsequent to alcohol withdrawal in ratsObjectiveTo evaluate behavioral changes in ADS rats after HHdT formula intervention.MethodsThe ADS models were set up through continuously feeding rats with low concentration alcohol. The rats were divided into the treatment group (TG), control group (CG) and normal group (NG). From day22on, the ADS rats in TG were given HHdT formula, those in CG were given purified water by gavage, while the rats in NF were given no intervention. On day29, all the ADS rats were withdrawn from alcohol, receiving only purified water instead of alcohol. The scores in terms of behavioral characteristics and Audiogenic seizure were assessed2h,6h,24h, and48h after alcohol withdrawal.ResultsScores of alcohol withdrawal behavior in CG were significantly higher than those in NG2h,6h, and24h after alcohol withdrawal (p<0.05), while the scores in TG were in between. The scores were not significantly different among the3groups48h after alcohol withdrawal (P>0.05)Experiment2Effects of HHdT formula on DA NAc subsequent to alcohol withdrawal in ratsObjectiveTo investigate NAc DA levels in ADS rats after HHdT formula intervention using HPLC-MS/MS technique. MethodsThe way to set up models and treatment protocol were same as the experimental1. HPLC-MS/MS technique was used to evaluate NAc DA levels of the high dose treatment group (HDTG), low dose treatment group (LDTG), control group (CG) and normal group (NG).ResultsNAc DA level in CG was the highest (2.14±0.32μg/g), that in NG was the lowest (0.96±0.38μg/g); the NAc DA levels of the treatment group showed no significant difference with HDTG at1.43±0.41μg/g and LDTG at1.50±0.28μg/g (p>0.05).更多还原