病证结合冠心病心绞痛气虚血瘀证研究

【作者】 陈忠良；

【导师】 王阶；

【作者基本信息】 中国中医科学院 ， 中医内科学， 2007， 硕士

【摘要】 冠心病是威胁人类生命的常见病和多发病。在西方国家中，冠心病成为致死的首要原因。在发展中国家，包括中国在内，其发病率和死亡率呈逐年上升趋势，并已成为致死的主要原因之一。探讨冠心病诊断方法和有效防治措施，降低冠心病发病率、死亡率和致残率已成为医学工作者研究的重要课题。本论文在梳理古代文献的基础上，检索近10年现代文献有关冠心病心绞痛的研究进展，明确气虚与血瘀、气虚血瘀与冠心病心绞痛的关系，总结气虚血瘀证的治则治法及方药。并通过流行病学临床调查研究，明确冠心病心绞痛气虚、血瘀及气虚血瘀证的分布特点，运用Logistic回归分析，确定气虚、血瘀及气虚血瘀的诊断依据。通过冠心病心绞痛证候与实验指标的关系研究，探讨气虚、血瘀、气虚血瘀的生物学基础。通过对有关冠心病心绞痛治疗的现代文献病例分析，选择符合冠心病心绞痛气虚血瘀证诊断且有明确疗效的病例，系统总结冠心病心绞痛气虚血瘀证常用药物、剂量范围、药物配伍、常用方剂等，探讨治疗气虚血瘀证的用药规律。1．现代文献研究冠心病心绞痛的病因与年老体衰、情志刺激、劳倦太过、饮食不节等，其病机多与阳虚、气虚、阴虚、寒凝、痰浊、气滞有关，其中气虚血瘀是冠心病心绞痛的基本病机。治疗冠心病心绞痛的常用代表方剂有：血府逐瘀汤、补阳还五汤、桃红四物汤、肾气丸、温胆汤、瓜蒌薤白半夏汤、丹参饮、小陷胸汤等。2．流行病学临床调查研究通过临床流行病学调查研究，搜集到经冠脉造影确诊的冠心病心绞痛病人297例。其中气虚者234例，占总病例的78.8％；血瘀者257例，占总病例的86.5％；气虚血瘀者201例，占全部病例的67.7％。研究表明，气虚和血瘀是冠心病心绞痛的最主要证候要素。分别以气虚、血瘀和气虚血瘀为因变量，以症状和体征为自变量，运用Logistic回归分析，筛选出气虚、血瘀、及气虚血瘀的诊断指标，确定诊断依据。血瘀诊断指标按相关系数大小排列依次是：舌脉青紫(15.7280)、瘀点斑(14.5488)、舌脉怒张(14.1818)、刺痛(13.7902)、绞痛(13.7743)、脉涩(13.5036)、舌脉紫红(12.6984)。气虚诊断指标按相关系数大小排列依次是：语声低微(9.6150)、倦怠乏力(8.8945)、自汗(8.2317)、活动诱发(8.1845)、面色萎黄(7.6159)、腰膝酸软(6.9995)、隐痛(5.6460)、舌胖大(5.2584)、气短(4.4093)。气虚血瘀诊断指标按相关系数大小排列依次是：语声低微(4.4851)、舌脉迂曲(3.6887)、舌脉青紫(2.4424)、倦怠乏力(2.2061)、舌脉紫红(1.9718)、胸痛(1.6425)、自汗(1.4813)、瘀点斑(1.2129)、气短(1.1010)、活动诱发(1.0591)。3．气虚血瘀的生物学基础研究本研究通过气虚、血瘀、气虚血瘀分别与D-二聚体(D-Dimer)、CD62P、纤维蛋白原(FIB)、肿瘤坏死因子(TNF)的关系研究，探讨冠心病心绞痛气虚、血瘀、气虚血瘀的病理变化特点。结果显示，气虚与非气虚两组的各项实验指标相比较，气虚组D-二聚体，CD62P，FIB均高于非气虚组，且存在显著性差异(P＜0.05或P＜0.01)，提示气虚与上述3项指标最相关。血瘀与非血瘀两组的各项实验指标相比较，血瘀组TNF、CD62P均高于非血瘀组，且有显著性差异(P＜0.05或P＜0.01)，提示血瘀与上述2项指标最相关。气虚血瘀与非气虚血瘀两组的各项实验指标相比较，气虚血瘀组D-二聚体，CD62P，FIB均高于非气虚血瘀组，且有显著性差异(P＜0.05或P＜0.01)，提示气虚血瘀与上述3个指标最相关。研究表明，气虚、血瘀、及气虚血瘀的病理变化各有特点。4．治疗气虚血瘀的用药规律研究以清华大学CNKI医院知识数据库为主，以冠心病+中医药疗法+气虚血瘀、心绞痛+中医药疗法+气虚血瘀、胸痹+气虚血瘀为检索词，查阅1997年10月至2006年10月国内的文献115篇。运用描述性统计方法(Descriptive Statistic)和聚类分析(Cluster Analysis)进行统计处理。①治疗气虚血瘀证最常用的中药中，益气药以黄芪最常用，其次是甘草／炙甘草、党参，再次是人参、茯苓／茯神等；活血药以丹参、川芎最常用，其次是赤芍、红花、当归，再次是三七、郁金、桃仁、元胡等。②分别统计出治疗气虚血瘀证的常用中药的剂量范围及平均用量，如黄芪用量范围100-15g，平均32.57g；党参45-10g，平均19.85g；丹参100-10g，平均23.72g；赤芍30-9g，平均13.95g；当归25-9g，平均13.92g，等。③治疗气虚血瘀证常用的方剂有主要有生脉散、冠心Ⅱ号、当归补血汤、丹参饮、瓜蒌薤白半夏汤、柴胡疏肝散等。④治疗气虚血瘀证常用的对药有：党参和白术、太子参和泽泻、蒲黄和香附、桃仁和红花、木香和黄连、砂仁和檀香、枸杞和生／熟地。3药组合有：人参、麦冬、五味子；甘草／炙甘草、丹参、葛根；降香、川芎、赤芍；三七、桂枝、白芍；柴胡、枳壳、桔梗。4药组合有：黄芪、当归、水蛭、地龙；瓜蒌、薤白、延胡索、郁金。4药以上组合有：陈皮、茯苓／茯神、半夏、竹茹、枳实、酸枣仁、远志。⑤冠心病心绞痛气虚血瘀证在临床上往往会同时兼有其它证候，故在益气活血药的基础上，许多专家都会根据病情、体质、四时变化等随证加减用药，有理气药、化痰药、安神药、解表药、利湿药等。更多还原

【Abstract】 Coronary disease is a disease that pose as the most important threats to human life.In western countries, Coronary disease is the most lethal reasons of death.In developing countries, including China, its disease rate and mortality rate were escalating on yearly basis.The discussion of diagnosis methods and the effective preventing and controlling measures of Coronary diseases, reducing the Coronary diseases incidence rate, mortality rate and crippling rate has become an important topic for the medical workers studies.This present paper in ancient literatures foundation, researched the near 10 years of modern literatures of related Coronary disease anginapectoris research progress, to clarify about Qi-deficiency and blood stasis, Qi-deficiency and blood stasis with the Coronary disease angina pectoris relations, summarize Qi-deficiency and blood stasis signs curing method and curing medicines. And through the epidemiology clinical investigation and study, to clarify about Coronary disease anginapectoris Qi-deficiency, blood stasis, Qi-deficiency and blood stasis signs distributed characteristic, utilizes the Logistic regression analysis, determining Qi deficiency, blood stasis, Qi-deficiency and blood stasis diagnosis basis. Through Coronary disease anginapectoris pattern and experimental indicators relational research, discussing Qi-deficiency, blood stasis, Qi-deficiency and blood stasis’s biological basis. Through analyzing to the related Coronary disease anginapectoris treatment in modern literature case of illness, choosing the Coronary disease anginapectoris Qi-deficiency and blood stasis sign diagnosis matching criteria and a clear curative effect cases of illness, systematically summarizing Coronary disease anginapectoris Qi-deficiency and blood stasis signs commonly used medicine, the dosage range, the medicine combining, commonly used formula and so on, discussing the treatment of Qi-deficiency and blood stasis signs and its medication rule.1．Modern literature researchThe Coronary disease anginapectoris cause of disease varies with the debility of old age, overacting of emotions, extreme fatigue, dietary irregularities and so on, its pathogenesis related with Yang-deficient, Qi-deficiency, Yin-deficient, congealing cold, phlegm turbidity, Qi-stagnancy, etc. From with, Qi-deficiency and blood stasis is the Coronary disease anginapectoris basic pathogenesis. Treatment of Coronary disease anginapectoris commonly used of formulas: House of Blood Stasis Expelling Decoction (血府逐瘀汤), Yang Supplementing Five-Returning Decoction (补阳还五汤), Peach Kernel and Carthamus Four-agents Decoction (桃红四物汤), Kidney Qi Pill (肾气丸) , Gallbladder-warming Decoction (温胆汤) , Trichosanthes Chinese Chives and Pinellia Decoction (栝蒌薤白半夏汤), Salvia Beverage (丹参饮), Minor Chest-Bind Decoction (小陷胸汤) etc.2．Epidemiology clinical investigation and studyThrough the clinical epidemiology investigation and study, collects the Coronary disease anginapectoris patients of 297 cases, which diagnosed by Coronary angiography. Qi-deficiency 234 examples, occupy the total case of illness 78．8%; Blood stasis 257 examples, occupy the total case of illness 86．5%; Qi-deficiency and blood stasis 201 examples, occupy the complete case of illness 67．7%. The research indicated that, Qi-deficiency and blood stasis is the Coronary disease anginapectoris most main symptoms essential factor.Respectively from Qi-deficiency, blood stasis, Qi-deficiency and blood stasis as the dependent variable, drafts its symptoms and body symptoms as the independent variable, utilizes the Logistic regression analysis, screens Qi-deficiency, blood stasis, Qi-deficiency and blood stasis diagnosis standards, determining its diagnosis basis.Blood stasis diagnosis standard according to the correlation coefficient size arrangement are in turn: tongue arteries purplish and blue (15．7280) , stasis speckle and spot (14．5488) , curled tongue arteries (14．1818) , stabbing pain (13．7902) , gripping pain (13．7743) , astringent pulse (13．5036) , tongue arteries purplish and red (12．6984) .Qi-deficiency diagnosis standard according to the correlation coefficient size arrangement are in turn: faint low voice (9．6150) , fatigue and lack of strength (8．8945) , spontaneous sweating (8．2317) , activity induced (8．1845) , withered-yellow facial complexion (7．6159) , limp aching lumbus and knees (6．9995) , dull pain (5．6460) , tongue enlargement (5．2584) , shortness of breath (4．4093) .Qi-deficiency and blood stasis diagnosis standard according to the correlation coefficient size arrangement are in turn: faint low voice (4．4851) , curled tongue arteries (3．6887) , tongue arteries purplish and blue (2．4424) , fatigue and lack of strength (2．2061) , tongue arteries purplish and red (1．9718) , chest pain (1．6425) , spontaneous sweating (1．4813) , stasis speckle and spot (1．2129) , shortness of breath (1．1010) , activity induced (1．0591) .3．Qi-deficient and blood stasis biological basic researchThis research through Qi-deficiency, blood stasis, Qi-deficiency and blood stasis separately with D-Dimer, CD62P, Fibrinogen (FIB), Tumor Necrosis Factor (TNF) relational research, discusses coronary disease anginapectoris Qi-deficiency, blood stasis, Qi-deficiency and blood stasis pathological change characteristics. The result showed that, Qi-deficiency compares with the non-Qi-deficiency, two groups of each experimental indicators, Qi-deficiency’s group D-Dimer, CD62P, FIB is higher than the non-Qi-deficiency group, also has significant differences (P < 0．05 or P < 0．01) , prompts Qi-deficiency and the above 3 standards are most related. Blood stasis compares with the non-blood stasis, two groups of each experimental indicators, blood stasis’s group TNF, CD62P are higher than the non-blood stasis group, also has significant differences (P < 0．05 or P < 0．01) , prompts blood stasis and the above 2 targets is most related. Qi-deficiency and blood stasis compares with the non-Qi-deficiency and blood stasis, two groups of each experimental indicators, Qi-deficiency and blood stasis’s group D-Dimer, CD62P, FIB is higher than the non-Qi-deficiency and blood stasis group, also has significant differences (P < 0．05 or P < 0．01) , prompts Qi-deficiency and blood stasis and the above 3 targets is most related. The research indicated that, Qi-deficiency, blood stasis, Qi-deficiency and blood stasis pathological changes has their own respective characteristics.4．Research of Qi-deficiency and blood stasis treatment with its medication rulePrimarily using Tsinghua University CNKI hospital knowledge database, by Coronary disease + Chinese medicine therapy + Qi-deficiency and blood stasis, Anginapectoris + Chinese medicine therapy + Qi-deficiency and blood stasis, Chest impediment + Qi-deficiency and blood stasis as the retrieval word, consulted from April, 1992 to October, 2006, consist of 115 domestic literatures. Utilizes Descriptive Statistic and Cluster Analysis statistical method in statistical processing.①The treatment Qi-deficiency and blood stasis sign most commonly used Chinese medicine includes: Ginseng Radix (人参) , Codonopsitis Radix (党参) , Astragali Radix (黄芪) , Honey-fried Licorice (炙甘草), Salviae Miltiorrhizae (丹参) , Ligustici Rhizoma (川芎) , Paeoniae Radix Rubra (赤芍) , Carthami Flos (红花) , Angelicae Sinensis Radix (当归) , Notoginseng Radix (三七) etc.②Separately counts the treatment of Qi-deficiency and blood stasis sign with commonly used Chinese medicine dosage scope and the average amount used, like Astragali Radix (黄芪) amount used scope 100-15g, averaging 32．57g; Codonopsitis Radix (党参) 45-10g, averaging 19．85g; Salviae Miltiorrhizae (丹参) 100-10g, averaging 23．72g; Paeoniae Radix Rubra (赤芍) 30-9g, averaging 13．95g; Angelicae Sinensis Radix (当归) 25-9g, averaging 13．92g etc.③The treatment of Qi-deficiency and blood stasis sign commonly used formula includes: Pulse-Engendering Powder(生脉散), Coronary noⅡ(冠心Ⅱ号), Tangkuei Blood-Supplementing Decoction (当归补血汤) , Salvia Beverage (丹参饮) , Trichosanthes Chinese Chives and Pinellia Decoction (栝蒌薤白半夏汤), Bupleurum Liver-Coursing Powder (柴胡疏肝散) etc.④The treatment of Qi-deficiency and blood stasis sign with its commonly used combination of medicines: Codonopsitis Radix (党参) and Atractylodis Ovatae Rhizoma (白术) , Pseudostellariae Radix (太子参) and Alismatis Rhizoma (泽泻) , Typhae Pollen (蒲黄) and Cyperi Rhizoma (香附) , Persicae Semen (桃仁) and Carthami Flos (红花) , Saussureae Radix (木香) and Coptidis Rhizoma (黄连) , Amomi Semen Seu Fructus (砂仁) and Santali Lignum (檀香) , Lycii Fructus (枸杞) and fresh/dried Rehmanniae Radix Exsicatta Seu Recens (生/熟地) . 3 medicines combinations includes: Ginseng Radix (人参) , Ophiopogonis Tuber (脉冬) , Schisandrae Fructus (五味子); Honey-fried Licorice (炙甘草), Salviae Miltiorrhizae (丹参) ,Puerariae Radix (葛根) ; Dalbergiae Lignum (降香) , Ligustici Rhizoma (川芎) , Paeoniae Radix Rubra (赤芍) ; Notoginseng Radix (三七) , Cinnamomi Ramulus (桂枝) , Paeoniae Radix Alba (白芍) ; Bupleuri Radix (柴胡) ,Aurantii Fructus (枳壳) , Platycodonis Radix (桔梗) . 4 medicines combinations includes: Astragali Radix (黄芪) , Angelicae Sinensis Radix (当归) , Hirudo Seu Whitmania(水蛭) ,Lumbricus (地龙) ; Trichosanthis Fructus (瓜蒌) ,Allii Bulbus (薤白) , Corydalis Tuber (延胡索) , Curcumae Tuber (郁金) . More than 4 medicines combination includes: Citri Exocarpium (陈皮) , Poria (茯苓) , Pinelliae Tuber (半夏) , Bambusae Caulis in Taeniam (竹茹) , Aurantii Fructus Immaturus (枳实) , Ziziphi Spinosi Semen (酸枣仁) , Polygalae Radix (远志) .⑤The Coronary disease anginapectoris Qi-deficiency and blood stasis sign in clinical often exists with other signs, therefore in basic of boosting Qi and invigorates blood, many experts according to the condition, physique, four season’s changes etc, could vary the medicine combinations along with the signs, such as: rectify Qi medicinal (理气药) , phlegm-transforming medicinal (化痰药) , nerve-calming medicinal (安神药), exterior-resolving medicinal (解表药), dampness-disinhibiting medicinal (利湿药) etc.更多还原