【作者】 陈明；

【导师】 赵国平；

【作者基本信息】 南京中医药大学 ， 中医医史文献， 2010， 博士

【摘要】 研究目的桂枝汤是《伤寒杂病论》开篇第一方,是调和营卫、血气、阴阳的总方,虽药仅五味,而应用范围之广、演变类方之多,实非它方所能及。桂枝汤方证即桂枝汤临床应用时的适应症及其病机,历代文献对此方研究较多。本文在总结历代医家经验的基础上,从数据挖掘的角度对此方方证进行研究。目的是为了揭示桂枝汤的多效多证,揭示桂枝汤的拓展应用的规律,桂枝汤方随证变的规律。从古今桂枝汤及其加减方的应用数据中挖掘桂枝汤方证的诊断标准,从而使桂枝汤方证规范化、客观化、标准化,指导临床应用。研究方法本文所研究的数据来源于①有《伤寒杂病论》(桂枝汤及其类方33首,涉及62条原文)。②《方剂大辞典》(桂枝汤及其加减方剂93首)③现代临床应用报道(应用桂枝汤及其加减方临床治案421例)。④相关医学著作的内容(39种医学专著,涉及医案92例)。在研究过程中,首先,对所采集的数据信息进行了规范处理,建立病证、症状、方剂、用药等相应的数据库,分别对《伤寒杂病论》、《方剂大辞典》及现代临床报道三类文献中主治病、症状、方剂、用药情况进行了统计。其次,采用文献研究法,对桂枝汤原方方证进行研究。运用因子分析的数据挖掘方法,分别对三类文献进行症状因子分析、用药因子分析,以此来揭示桂枝汤及其加减方方证的病机、变化证型及药物配伍规律。此外,还运用双向关联规则的数据挖掘方法分别对《伤寒杂病论》、《方剂大辞典》及现代临床报道中病—方、症—方、病—桂芍比及药对之间的关联关系进行分析。以此来揭示桂枝汤及其加减方病—证—方—药之间的关系。在本文研究过程中,引入了族类方的概念,以此来形象地揭示桂枝汤与其类方之间的血缘亲疏关系。研究结果1、三类文献症状因子分析结果反映了桂枝汤及其加减方具有外感营卫不和、心阳虚、肢体痹痛、脾胃不和、气上冲等证侯特点。其中,《方剂大辞典》及现代临床应用的症状因子分析结果还反映了营卫失和、阴阳两虚的证侯特点。2、三类文献用药因子分析结果有交叉,基本体现了桂枝汤原方、桂枝加厚朴杏子汤、桂枝加龙骨牡蛎汤、当归四逆汤、苓桂术甘汤、桂枝加葛根汤、桂枝加附子汤、黄芪建中汤、桂枝新加汤等桂枝汤的药物加减规律。此外,《方剂大辞典》及现代临床应用还体现了柴胡桂枝汤、桂枝羌活汤、桂枝新加汤、桂枝甘草汤等方剂配伍规律。3、三类文献病—方关联分析结果显示桂枝汤与外感发热、精微不固类疾病密切相关,小建中汤、黄芪建中汤与虚劳类、腹痛类疾病密切相关。现代临床应用研究结果还提示桂枝汤与皮肤病、肢体痹痛类疾病密切相关。4、根据三类文献症—方关联分析结果相关度值的高低推论桂枝汤证的主证为脉浮缓、汗出。兼证为发热、恶风、恶寒、头痛、苔薄白、二便调。根据现代文献症状与方剂相关度表还可以推论柴胡桂枝汤、当归四逆汤、桂枝加附子汤、桂枝麻黄各半汤等桂枝汤加减方的主证及兼证。5、三类文献病—桂芍比关联分析结果显示《伤寒杂病论》中桂芍比1：1出现的较多,达61%。《方剂大辞典》中桂芍比1：0出现较多,达33%,而现代临床应用中,应用比例较高的依次为桂芍比1：1、1：0、1：2、5：3。桂芍比1：1多用于外感表证、肢体痹痛类病证。桂芍民1：0多用于心阳虚类及气上冲类病证。桂芍比1：2多用于腹痛类及虚劳类病证。桂芍比5：3用于气上冲类病证。6、三类文献药对关联分析结果提示在古代文献中原方两两配对应用情况较普遍,而现代临床应用中,由于药物加减较多,故提示的药对多为加减后两两出现的药物。结论通过以上研究方法的运用,本文归纳出桂枝汤原方方证、桂枝汤加减方的方证、桂枝汤加减方的构效关系规律及桂枝汤加减方的量效关系规律。1、桂枝汤原方方证有四(1)太阳表证；(2)脾胃不和兼表证；(3)未感外邪的营卫不和证：(4)妊娠恶阻证。桂枝汤的基本病机为营卫不调。此外,本文还归纳出桂枝汤的体质特点。2、桂枝汤加减方证候可分为七大类,分别为(1)外感发热类(2)肌肉痉挛类(3)肢体痹痛类(4)腹痛类(5)气上冲类(6)心阳虚类(7)精微不固类。3、桂枝汤及其加减方的构效关系规律：桂枝汤原方由桂枝甘草汤及芍药甘草汤两张基础方构成。根据三类文献用药因子分析结果,归纳出20张桂枝汤加减方的药物加减规律及其所主治的病证,并对其各自与桂枝汤原方的族类关系进行了分析。4、桂枝汤及其加减方的量效关系规律：桂芍比1：1多为桂枝汤原方,或是桂枝汤亲族、近族,解表合里,调和营卫；桂芍比1：0多为桂枝汤的远族,温通心阳、平冲降逆；桂芍比1：2多为桂枝汤的变族,温阳和络、缓急止痛；桂芍比5：3解肌通阳、平冲降逆。最后,本文对桂枝汤的调和作用、桂枝汤的煎服法、现代药理研究进行了讨论。分析本文所运用的数据挖掘方法的先进性及其不足之处。同时,对今后深层次的研究进行了展望。创新之处将双向关联规则算法及因子分析方法同时运用于经方的方证研究。并通过症状与方剂关联度结果表来推测方剂的主证及兼证,使方剂的主证、兼证标准更加客观化。运用族类关系来分析桂枝汤与其类方的关系,使之形象化、系统化。更多还原

【Abstract】 Objective:《GUIZHI DECOCTION》is the first prescription in "Treatise on Cold Pathogenic and Miscellaneous Diseases", which is the general prescription for harmonizing yingfen and weifen, qi and blood, yin-yang. Although it only consists of five herbal medicines, no other prescription can be comparable in the aspects of wide range of application and variety of categorized formula. The prescription and syndrome of GUIZHI DECOCTION is namely its clinical indications and pathogenesis, which has been researched widely in the literatures of past dynasties. In this thesis, based on the experience of herbalist doctors of past dynasties, it uses the data mining technology to research the prescription and syndrome of GUIZHI DECOCTION, which aims to unveil the multi indications and multi functions, and the application rule of extending use, the rule of prescription modification with syndrome. Mining the diagnosis standard of GUIZHI DECOCTION from application from GUIZHI DECOCTION and its modification can make the prescription and syndrome of GUIZHI DECOCTION standardization, objective so as to guide clinic application.Methods:The research data in this thesis come from 1) "Treatise on Cold Pathogenic and Miscellaneous Diseases "(33 cases of GZT and its categorized formula, related to 62 items of original text); 2) "Prescription Dictionary"(93 prescriptions of GZT and its modification); 3) Modern clinical application(421 clinical cases treated by GZT and its modification);4) Relevant medical literatures (39 medical literatures, covering 92 clinical cases). In our research, the data is processed by standardization first, and the databases of symptom, prescription, treatment with medicine are built respectively, the prescription, symptom and treatment with medicine in above three types of literatures are made statistic respectively. Then, reference research method is used to research the prescription and symptom of《GUIZHI DECOCTION》,and factor analysis is used to analyze for above three types of literature, which is to reveal the pathogenesis、varied syndrome and the law of herbal synergy of GUIZHI DECOCTION and its modifying prescription. Besides, the bi-direction association rule is used to analyze the association relationship of disease -prescription、syndrome-prescription、disease-the rate of GuiZhi Shaoyao dosage in above three types of literature, which is to reveal the relationship among the disease-syndrome-prescription-herbal medicine for GUIZHI DECOCTION and its modifying prescription. In our research, the concept of the family categorized formule is introduced so as to reveal the relationship among GUIZHI DECOCTION and other categorized formula。Result:1 Factor analysis results on symptom from three kinds of literature reflect that the GUIZHI DECOCTION has following features on syndrome:exogenous disease of disharmony between nutrient qi and defensive qi, devitalization of heart yang, body pantalgia, syndrome of incoordination between spleen and stomach, syndrome of qi rushing upward, where factor analysis results of Prescription Dictionary and Modern clinical application reflect the syndrome features on disharmony between nutrient qi and defensive qi, deficiency of both yin and yang.2 The factor analysis results on treatment with medicine from three kinds of literature are overlapped in certain degree, which reflects the medicine modifying rules of GUIZHI DECOCTION categorized formula, such as guizhi decoction, guizhi houpu xingzi decoction, guizhi longgu muli decoction, danggui sini decoction, linggui shugan decoction, guizhi gegen decoction, guizhi fuzi decoction, huangqi jianzhong decoction,guizhi xinjia decoction. Beisdes, the factor analysis results on treatment with medicine from Prescription Dictionary and Modern clinical application also reflects the herbal synergy rules of caihu guizhi decoction, guizhi qianghuo decoction, guizhi xinjia decoction, guizhi gancao decoction etc.3 The association analysis on disease-prescription from three kinds of literature show the GUIZHI DECOCTION has close association with exogenous disease of fever, failure of keeping essence. Xiao jianzhong decoction, huangqi jianzhong decoction has close association with consumptive diseas and abdominal pain. The results from Modern clinical application also indicate that GUIZHI DECOCTION has close association with dermatosis and body pantalgia.4 Based on the association analysis on syndrome-prescription from three kinds of literature, the principal syndrome of GUIZHI DECOCTION inferred from the correlation degree is floating and moderate pulse, sweating. The complication syndrome is fever, aversion to wind, aversion to cold, headache, thin and white fur, natural stool and pee. According to the correlation degree on syndrome-prescription from modern literatures, the principal syndrome and the complication syndrome can inferred for modifying prescription of GZT, such as caihu guizhi decoction, danggui sini decoction, guizhi fuzi decoction, guizhi mahuang decoction etc.5 The association analysis on rate of Guizhi Shaoyao dosage reveals that the frequency of this rate with 1:1 is high in "Treatise on Cold Pathogenic and Miscellaneous Diseases" with 61%; the frequency of this rate with 1:0 is high in "Prescription Dictionary" with 33%, and for modern clinical application, the this rate with high frequency is 1:1,1:0,1:2,5:3. The rate with 1:1,1:0,1:2,5:3, is mainly used for exogenous disease of superficies syndrome and body pantalgia, devitalization of heart yang and syndrome of qi rushing upward, consumptive diseas and abdominal pain, syndrome of qi rushing upward respectively.6 The association analysis on couplet medicines of three kinds of literature cues us that the two herbal synergy is very popular in ancient literatures, but in modern clinical application, due to herbal modifying in prescription, the hinted couplet medicines is the two herbal after modifying.Conclusion:Based on above research, some rules are summed up for GUIZHI DECOCTION and its modifying prescription, such as the relationship between prescription and syndrome, effect and quantity, effect and composition. The principal prescription and syndrome of GUIZHI DECOCTION and its modifying prescription can be concluded as follows:1 The syndrome of GUIZHI DECOCTION original prescription has four aspects: (1) Taiyang superficies syndrome (2)syndrome of incoordination between spleen and stomach with superficies syndrome (3)disharmony between nutrient qi and defensive qi without external cause (4)hyperemesis gravidarum. The pathogenesis of GZT is disharmony between nutrient qi and defensive qi. Besides, the applicable constitution feature of GZT is also summed up.2 The syndrome of modifying prescription of GUIZHI DECOCTION can be grouped into 7 types, they are (1)exogenous disease of fever, (2)muscle spasm, (3) body pantalgia, (4) abdominal pain, (5) syndrome of qi rushing upward, (6) devitalization of heart yang, (7) failure of keeping essence.3 The rule of relationship between component and effect of GZT:The original prescription of GZT is based on the two prescription of guizhi gancao decoction and shaoyao gancao decoction. By the factor analysis results, herbal modifying rule of 20 prescriptions of GZT and their principal symptom are concluded, and their family relationship with original prescription of GZT is also analyzed.4 The rule of relationship between effect and quantity of GZT and its modifying prescription is as follows:the rate of Guizhi Shaoyao dosage with 1:1 is mainly from original prescription or cognation of GZT, which has the indication of expelling pathogens from both interior and superficies, harmonizing yingfen and weifen. The rate of Guizhi Shaoyao dosage with 1:0 is mostly the far family of GZT, which has the indication of warmly invigorating heart yang, activating qi for lowering adverse qi. The rate of Guizhi Shaoyao dosage with 1:2 is mostly the modifying family of GZT, which has the indication of warming yang and removing obstruction in collaterals, relieving spasm and relieving pain. The rate of Guizhi Shaoyao dosage with 5:3 has the indication of expelling pathogenic factors from muscles and warming yang, activating qi for lowering adverse qi.Finally, At the end, the harmonizing effect, the decoction method and modern pharmacody of GZT are discussed. Meanwhile, the advantage and disadvantage of data mining technology used in this thesis are discussed, and research in the future is prospected.Innovation:The bi-direction association rule and factor analysis are used to research the prescription and syndrome of classical prescription at same time. Besides, the correlation degree of syndrome and prescription is used to infer the principal syndrome and complication syndrome of prescription, which makes the standard of the principal syndrome and complication syndrome of prescription more objective. The family cluster relation is used to analyze GZT and its categorized formula so as to makes the research visualization, systematic.更多还原