【作者】 陈方敏；

【导师】 彭万年；

【作者基本信息】 广州中医药大学 ， 中医临床基础， 2010， 博士

【摘要】 糖尿病心脏病(Diabetic Cardiopathy, DC)是糖尿病最重要的远期并发症之一,包括糖尿病心脏微血管病变、大血管病变、心肌病变、心脏植物神经功能紊乱等。糖尿病远期心血管并发症已成为目前对糖尿病人远期生存的主要威胁和病死率的首位原因。目前以中医理论为指导,在实验研究和临床研究上都取得了一定的成效,初步明确了本病的中医病因病机和辨证治疗方法,并研制出行之有效的治疗方药。西医虽然治疗糖尿病心脏病有一定疗效,但西药的副作用较大,且病情反复。中医通过辨证论治有效提高患者机体的抗病能力,对糖尿病并发心血管疾病起到了一定的控制和改善作用,且提高了患者的生存质量,这是治病求本的方法。这也正是中医药治疗糖尿病心脏病的优势所在。目前治疗糖尿病心脏病的中成药种类很少,中医古籍记载了许多治疗消渴病并发心病的方药,且现代药理研究表明部分中药既能降血糖又能对心血管疾病起到一定的防治作用。本研究的主要内容和结果如下：一、糖尿病心脏病中医文献研究1.古代中医文献研究：通过对历代文献的整理,把古代医家对消渴病并发心病的论述进行归类,总结本病病因为禀赋虚弱、饮食不节、过服丹石、情志失调、劳欲过度,病机为肾阴亏虚、心火亢盛,消渴致瘀、瘀血阻络,脾虚生痰、痰浊内阻。从相关医家方药的应用,总结出本病的治法为益气养阴、清泻心火法,镇惊定志、养心安神法,心肾同治法,健脾化湿、行气利水法。并对膈消、肺消、上消等相关概念进行辨析。2.现代中医文献研究：(1)中医命名的探讨：本病的命名可分为消渴病心病、消渴病·胸痹心痛、消渴病·心悸怔忡、消渴病·支饮水肿。(2)病因病机的探讨：发病初期：心阴不足、心阳气不足；发病中期：心血瘀阻、痰浊内阻、瘀热互结；发病后期：心肾阳虚、水饮凌心。(3)糖尿病心脏病的中医药治疗进展：辨病分型论治；分期辨证；中成药治疗；实验研究；单味药研究。(4)糖尿病心脏病西医研究概况。二、方药证治规律研究探讨古今文献中治疗糖尿病心脏病的方剂和中药的应用情况,通过运用现代统计学方法,对方药进行统计分析,探索中医药治疗本病的组方、药物配伍及证治规律。(一)古代方药证治规律研究1.研究方法古代方剂的选择以《中医方剂大辞典》为主要检索目标,自东汉张仲景的《伤寒论》等经典医籍,至清末民国期间的有关治疗消渴”并发的“心悸”、“心闷”、“心烦”、“心痛”、“怔忡”等心病症状者方药的文献资料都列入收集范围。规范数据,建立数据库,运用频数分析、聚类分析等统计学方法,总结方药证治规律。2.研究结果本研究古代方剂共涉及中药217种,明清以前共涉及152首方剂；明清时代共涉及88首方剂,合计240首方剂。古代方剂中出现的高频次药物依次有：麦冬,炙甘草,人参,黄连,知母,栝楼根,生地,黄芩,茯苓,甘草,石膏,竹叶,葛根,黄芪,赤茯苓,五味子,熟地,肉桂,茯神,白芍,桑白皮,升麻,牡蛎。古方治疗消渴病心病频数在前5位的药物类别是补虚药、清热药、化痰止咳平喘药、解表药、利水渗湿药；药物药性频率较高的是寒、温、平；药味频率较高的是甘、苦、辛；古方药物归经频数最高的前六经依次是肝、肺、胃、心、脾、肾。聚类分析结果示古方消渴病心病治疗多为苦寒泻下、滋阴清热、健脾祛湿、补脾益肾为主,用药甘温补益、健脾祛湿利水为主。(二)现代方药证治规律研究1.研究方法现代方剂的选择以维普数据库为主要检索途径,结合图书手工检索方式。对学术期刊杂志及专科书籍近20余年来所报道的中医药治疗DC的有关文献进行筛选。对所载主治病证中为“消渴病”并发“胸痹、心痛、心悸、怔忡”或“糖尿病”并发“冠心病、心肌病变、心律失常、心脏自主神经病变”等相关病证者均可纳入。规范数据,建立数据库,运用频数分析、聚类分析等统计学方法,总结方药证治规律。2.研究结果本研究分为治疗糖尿病冠心病方剂和治疗糖尿病心脏病方剂两个类别进行研究,共涉及223味中药。治疗糖尿病心脏病方剂共275首,其中治疗糖尿病冠心病方剂共120首。治疗糖尿病心脏病方剂出现的高频次药物依次有：丹参,黄芪,麦冬,生地,五味子,川芎,茯苓,太子参,葛根,当归,人参,天花粉,赤芍,玄参,山药,黄连,红花,半夏,瓜蒌,桂枝。治疗糖尿病冠心病方剂出现的高频次药物依次有：丹参,黄芪,麦冬,生地,五味子,川芎,茯苓,当归。今方治疗糖尿病心脏病频数在前5位的药物类别是补虚药、清热药、活血化瘀药、理气药、利水渗湿药。今方药物药性频率较高的是寒、温、平；药味频率较高的是甘、苦、辛。今方药物归经频数最高的前六经依次是肝、胃、脾、肺、心、肾。聚类分析结果示糖尿病心脏病治疗多为活血化瘀、行气止痛、养心安神、温阳通痹、滋阴清热、燥湿化痰为主。证型有气阴两虚、肝肾阴虚、心脾两虚、心肾阳虚、心脉瘀阻、痰气阻脉、阴寒凝滞、瘀热互结、水饮凌心。三、结论1.通过药物类别频数分析可知,治疗糖尿病心脏病的药物大多为补益药物,佐以清热祛湿、活血化瘀、健脾祛痰、行气利水的药物。这是由糖尿病心脏病大多为本虚标实,夹痰夹瘀决定的。2.通过药物性味频数分析可知,治疗糖尿病心脏病药物多为甘温,配伍以苦寒,甘温补益、苦寒降下与消渴的本虚标实,夹痰夹瘀热的病机相符。3.通过药物归经频数分析可知,治疗糖尿病心脏病的药物多以入肝经、胃经为主,其次为脾经、肺经、心经、肾经。由此可见,中医治疗DC多从疏解肝气、清泻胃热、健脾、调补心肾入手。4.治疗糖尿病心脏病需要针对不同患者具体辨证论治,而不能局限于应用某一种或某几种药物或方剂进行治疗,只有坚持整体观念和辨证论治的原则,才可有效的提高糖尿病心脏病的临床疗效。通过本研究,旨在奠定治疗DC的中医文献学基础,探讨DC的病因病机及方药证治规律,为防治DC的临床用药提供依据。更多还原

【Abstract】 Diabetic Cardiopathy (DC) is one of the most important complications of diabetes, including diabetic cardiac microvascular disease, macrovascular disease, cardiomyopathy and cardiac autonomic dysfunction. Cardiovascular complications of diabetes have become the main threat to long-term survival and the first reason of mortality in patients with diabetes. At present, under the guidance of traditional Chinese medicine theory, some achievements have been made in the experimental research and clinical research and causes and pathogenesis of the disease and differentiation therapy have been made clear initially. Effective prescriptions for treatment have been developed. Although the western medicine in treating DC has much significant effects, the medicine has increased side effects and the illness always relapses. Through syndrome differentiation treatment, Chinese medicine can improve patients through the body’s resistance to diseases and it has played a certain role in the control and improvement of the DC disease. What’s more, it has improved the quality of life of patients, which is incomparable by western medicine. At present, the types of Chinese prepared medicine for treating DC are rare. Many prescriptions in treating DC have been recorded in the Chinese classical literature and pharmacological studies show that some of the Chinese medicine can not only lower blood sugar but also play a role on prevention and treatment of cardiovascular disease. The main contents and results of this study are as follows:1 Study on Chinese medical literature of DCⅠStudy on Chinese classical literatureThrough sorting out the classical literature in all ages, classifying the discussions of ancient physicians about DC, and making the conclusion that the causes of DC are weak endowment, improper diet, over-serving elixir, emotional disorders, over working and sexual life and the pathogenesis are deficiency of kidney yin, exuberance of heart fire, blood stasis obstrucing the collaterals, phlegm due to spleen deficiency and phlegm obstrucing. According to the application of the related prescriptions, the therapies of DC are summed up by nourishing qi and yin, clearing the heart fire, relieving convulsion, tranquilizing by nourishing the heart, both treating the heart and the kidney, eliminating dampness by invigorating the spleen and activating qi to excrete water. Besides, some related terminologies like "ge-xiao"、"fei-xiao"、"shang-xiao" have been discriminated.ⅡStudy on modern Chinese medical literature of DC(Ⅰ)Approch to the Chinese medical name of DC:the naming of DC can be divided into Diabetes·heart disease, Diabetes·chest pain, Diabetes·palpitations, Diabetes·diaphragm retention of fluid and edema.(Ⅱ)Approch to the etiology and pathogenesis:in the early stage:deficiency of heart yin,lack of heart yang; in the middle stage:heart blood stasis, phlegm obstrucing and accumulation of blood stasis and heat; in the later stage: yang deficiency of heart and kidney, water and fluid invading the heart.(Ⅲ)Therapeutical development of Chinese medicine for DC:differentiation therapies for different syndromes; differentiation syndromes for different stages; Chinese prepared medicine treatment; experimental study; study on the single herb.(Ⅳ) Development of research on DC by western medicine.2 Study on the law of differentiation therapies and prescriptionsTo explore the application of Chinese medicine and prescriptions of DC treatment in the ancinent and modern literature, the statistical analysis is used to study the law of compatibility of prescriptions and differentiation therapies in the treatment of DC by Chinese medicine.ⅠStudy on the law of classical differentiation therapies and prescriptions (Ⅰ) MethodsThe choice of the ancinent prescriptions depends on the Dictionary of Chinese Medical Prescriptions as the main retrieval. The classsical literature is chosen from Shanghan Lun written by Zhang Zhongjing in the Donghan dynasty to the late Qing period. The literature of prescriptions about heart syndromes like palpitation, irritancy and chest pain is chosen to the research. Then make the data standard, establish the database and use the statistical methods like frequency analysis and cluster analysis to explore the law of differentiation therapies and prescriptions.(Ⅱ) ResultsThe ancient precriotions in this study include 217 kinds of Chinese medicine involving 152 prescriptions before the Ming and Qing dynasties, 88 prescriptions in the Ming and Qing dynasties, for a total of 240 prescriptions. The medicine of high frequency appearing in the ancient prescriptions is:Radix ophiopogon, Baked Licorice, Ginseng, Coptis, Anemarrhenae, kirilowii root, raw land, skullcap, Tuckahoe, licorice, gypsum, bamboo root, radices puerarire, astragalus, red Poria, Schisandra, Rehmannia, Cinnamon, Fu Shen, white peony root, Morus alba, Cimicifuga, oysters.The frequency of previous five of medicine categories in the ancient prescriptions is tonic herbs, herbs for clearing away heat, herbs for eliminating phlegm and stopping cough, herbs for relieving exterior syndrome, herbs for excreting water and dampness; the high frequency of medical potency is cold, warm and ping; the high frequency of medical taste is sweet, bitter and pungent; the high frequency of meridian tropism is liver, lung, stomach, heart, spleen and kidney.The results of cluster analysis show that the DC therapies of the ancient prescriptions are clearing away heat, nourishing yin, strengthening the spleen to eliminate dampness and strengthening the spleen and kidney. The medicine is some kinds of sweet and warm for nourishing and strengthening the spleen to eliminate dampness.ⅡStudy on the law of modern differentiation therapies and prescriptions(Ⅰ)MethodsThe choice of the modern prescriptions depends on the VIP database as the main retrieval, combining with manual retrieval methods. The literature is screened from the academic journals and specialist books for the past 20 years reported about the medical treatment of DC. The related diseases and syndromes like chest pain, palpitations, or coronary heart disease, cardiomyopathy, arrhythmia, cardiac autonomic neuropathy are chosen for research. Then make the data standard, establish the database and use the statistical methods like frequency analysis and cluster analysis to explore the law of differentiation therapies and prescriptions. (Ⅱ) ResultsThis research includes two categories:the prescriptions of diabetic coronary heart disease and the prescriptions of DC, involving a total of 223 herbs. The prescriptions of DC are 275, involving prescriptions of diabetic coronary heart disease 120. The medicine of high frequency appearing in the modern prescriptions is Radix salvia miltiorrhiza, astragalus, Radix ophiopogon, Radix rehmannia, schisandra chinensis, rhizoma chuanxiong, Poria, Radix pseudostellaria, radices puerarire, angelica, ginseng, radices trichosanthis, red peony root, Scrophulariaceae, yam, berberine, safflower, Breit, Trichosanthes and cinnamomum ramulus. The medicine of high frequency appearing in the prescriptions of diabetic coronary heart disease is Radix salvia miltiorrhiza, astragalus, Radix ophiopogon, Radix rehmannia, schisandra chinensis, rhizoma chuanxiong, Poria and angelica.The frequency of previous five of medical categories in the modern prescriptions is tonic herbs, herbs for clearing away heat, herbs for removing blood stasis, herbs for regulating qi flow and herbs for excreting water and dampness. The high frequency of medical potency is cold, warm and ping. The high frequency of medical taste is sweet, bitter and pungent. The high frequency of meridian tropism is liver, stomach, spleen, lung, heart and kidney.The results of cluster analysis show that the DC therapies of the modern prescriptions are removing blood stasis, activating qi to relieve pain, tranquilizing by nourishing the heart, warming the yang qi, nourishing qi, eliminating dampness and resolving phlegm. The syndromes are deficiency of qi and yin, yin deficiency of liver and kidney, both deficiency of heart and spleen, yang deficiency of heart and kidney, blood stasis in the heart meridian, phlegm and qi obstructing the meridian, stagnation of yin-cold, accumulation of blood stasis and heat and water and fluid invading the heart.3 ConclusionⅠAccording to the frequency analysis of medical categories, the medicine of DC treatment is mostly tonic herbs, combining with herbs for clearing heat and removing dampness, promoting blood circulation, strengthening the spleen to eliminate dampness and activating qi to excrete water. This is decided by the pathogenesis of DC, the principal deficiency and sthenia of pathogenic factors like phlegm and blood stasis. ⅡAccording to the frequency analysis of medical potency and taste, the herbs for treating DC are sweet and warm, compatibility with the bitter and cold, sweet and warm for nourishing, bitter and cold for eliminating heat. This is the same with the pathogenesis of DC, the principal deficiency and sthenia of pathogenic factors like phlegm and blood stasis.ⅢAccording to the frequency analysis of meridian tropism, the meridian tropism of herbs for treating DC is mainly liver meridian and stomach meridian and the secondary is spleen meridian, lung meridian, heart meridian and kidney meridian. It can be seen that the treatments of DC by Chinese medicine are dispersing the depressed liver-energy, clearing away stomach heat, strengthening the spleen and nourishing the heart and the kidney.ⅣThe treatment of DC needs differentiation therapies according to different patients, and it should not be limited to a particular application or certain kinds of prescriptions for treatment. The clinical efficacy of DC can improve effectively only by adhering to the overall concepts and principles of differentiation therapies. This research aims to lay the foundation of Chinese medical literature, explore the etiology and pathogenesis of DC and the law of differentiation therapies and prescriptions and provide the basis for clinical medicine in the prevention and treatment of DC.更多还原