【作者】 韩永刚；

【导师】 王永炎； 高思华； 冯兴中；

【作者基本信息】 中国中医科学院 ， 中医基础理论， 2008， 博士

【摘要】 糖尿病(消渴病)是临床常见病、多发病。近年来,随着我国国民经济的快速发展,人们生活水平的不断提高,生活压力的不断加大,糖尿病的发病率逐年升高,日益受到医务工作者和普通百姓的重视。目前在控制血糖方面西药疗效较显著,但存在着副作用大、改善临床表现差的缺点,而中医药在改善糖尿病患者临床表现、提高生活质量、预防和减少并发症等方面存在着独特的优势。因此,在中医学基础理论指导下,继续研究治疗糖尿病的高效低毒的中医方药,具有重要的现实意义和临床应用价值。论文共分文献综述、理论研究和临床研究三部分。文献综述部分,首先总结了目前中医界主流观点认糖尿病(消渴病)为阴虚燥热为主的病机认识和三消分治为主的治疗模式,进而分别从按照病位论治(包括从肝论治、从脾论治、从肾论治、从心论治、数脏腑兼治),按照病因或病理产物论治(包括从痰湿论治、从瘀论治、从痰瘀论治、从毒论治、从气论治等),其他理论和方法(例如玄府理论)等角度,论述了古今论治消渴病的理论和方法。理论研究部分,阐释了开阖枢理论与糖尿病(消渴病)的关系。开阖枢理论起源于《黄帝内经》,其原始意义是对门户的结构及其功能的完整描述。《黄帝内经》将开阖枢从门户理论延伸扩展为阳气升降出入理论,即人体阳气在门户升降出入,其工作机制是开阖枢。人体有两扇门,一扇是三阳主宰的在表的阳门,一扇是三阴主宰的在里的阴门。每扇门都有各自的开阖枢,即三阳的阳门“太阳为开,阳明为阖,少阳为枢”;三阴的阴门“太阴为开,厥阴为阖,少阴为枢。”阳门、阴门的开、阖、枢都决定于阳气的升降出入,因为阴阳之间是阳主阴从的关系,即阳为主导,阴为随从,二者间是以阳为主导的动态平衡关系。这一理论在《伤寒杂病论》中得到了发展和具体应用。论文中论述了开、阖、枢的功能特点,即开以升发外散为主,阖以沉降内入为主,枢以协调开阖为主。开、阖、枢三者是一个完整而统一的整体,相互协调,相互为用。进而论述了开阖枢理论实质内涵和开阖枢病理状态下的临床表现。继而揭示了人体两大枢机,即少阳为阳枢,主司调节阳气在表之升降出入;少阴为阴枢,主司调节阳气在里之升降出入。少阳阳枢与少阴阴枢在生理上密切联系,相互作用,在病理状态下则相互影响。相对应地,小柴胡汤、四逆散为张仲景调节阴阳两大枢机的主方,论文中论述了两方的应用和方解,提出柴胡为“调枢圣药”的观点。继而从八个方面进行论述,糖尿病(消渴病)的发生发展与人体阳气“开阖枢”失调密切相关。导师王永炎院士根据自身长期临床、科研的结果,提出糖尿病(消渴病)的发病关键在于枢机不利。并依据糖尿病(消渴病)所处的时期不同,枢机不利有所偏重,即疾病早、中期以少阳枢机不利为主,晚期以少阴枢机不利为主。因此,治疗糖尿病(消渴病)的关键在于调理两大枢机,枢机调则三阴三阳的阳气升降出入正常。王院士的柴胡调枢汤就是以小柴胡汤、四逆散为基础,结合其临床经验而拟定,抓住了糖尿病(消渴病)的发病关键,在此基础上随症加减,枢机得调则消渴自止。临床研究部分,观察了柴胡调枢汤治疗糖尿病的临床疗效和安全性。将患者随机分为治疗组、对照组各32例,对照组单用二甲双胍,治疗组在二甲双胍治疗的基础上加用柴胡调枢汤随症加减,治疗8周,观察治疗前后空腹血糖、餐后2小时血糖、糖化血红蛋白、中医症状及血常规、尿常规、便常规、肝功能、肾功能、心电图的变化。结果:经Ridit检验和重复测量的方差分析,治疗组对于空腹血糖、餐后2小时血糖、中医症状总积分、疾病疗效的疗效均好于对照组;而对于糖化血红蛋白的疗效,两组间差异不显著。通过综合分析,认为“柴胡调枢汤+二甲双胍”对于2型糖尿病的主、客观指标疗效均优于单纯应用二甲双胍,并且具有很好的安全性。由此可见,基于开阖枢理论创立的柴胡调枢汤治疗糖尿病具有很好的疗效和安全性,值得进一步临床推广应用。最后得出结论:“阳主阴从”思想是包括中医在内的传统文化认识宇宙、把握万物的关键;“开阖枢”理论是传统中医解读生命、治疗疾病的重要理论;糖尿病(消渴病)核心病机是枢机不利;少阳、少阴枢机不利证的临床表现存在复杂性和双重性;柴胡调枢汤治疗糖尿病(消渴病)的关键在于调阳理枢。本研究首次将“开阖枢”理论应用于2型糖尿病的临床研究中,突出了中国传统儒释道文化和中医注重阳气的观点。深化了中医对糖尿病病机的认识,为临床治疗糖尿病提供了新思路,提出治疗糖尿病(消渴病)的关键是“调阳理枢”,创新和丰富了糖尿病(消渴病)的病机学说和治疗学说。更多还原

【Abstract】 Diabetes is a common and frequently occurring disease in clinic. And it can heavily influence people’s work and living. In recent years, the incidence of diabetes is increasing year after year along with our country’s national income enhance fleetly, resident standard of living improved constantly, the changing of people’s life style, and living pressure increase continually. Average people and medical affairs operator are more and more attach importance to diabetes than before. At present, the sugar reducing medicine commonly used in clinical practice has definitely and affirmatively curative effect in controlling blood sugar. At the same time, Western medicine has its disadvantage, for instance, badly effect in improving symptom and huge side-effect. However, Traditional Chinese Medicine (abbreviation: TCM) has its own unique advantage, for example, improving diabetes sufferer symptom and enhancing their living quality, prevent and cure subsequent disease of diabetes. Therefore, the research of how to prevention and cure diabetes has become an important thing, especially in researching and exploring new medicine for diabetes under the guidance basic theory of TCM. This work has significant practical meaning and clinical application value.There are three parts in the thesis: document reviews, theoretic research and clinical research.Document reviews: At first, we summarized current mainstream viewpoint of TCM about diabetes’s pathogenesis key at yin-deficiency and dryness-heat, its primary therapeutic model is Sanxiaofenzhi. And then we discourse upon Diabetes’s deferent treatment theory and method from ancient to modern. For example, Diabetes treated according the location of disease (including Diabetes treated according the liver or spleen or kidney or heart or several organs) or Causes and pathological products (including Diabetes treated according phlegm-dampness or blood stasis or poison or Qi), and others treatment method (For instance, Diabetes treated according Xuanfu.)Theoretic research: We explained the relation between traditional theory of "Open, Close and Axis" and diabetes. The theory of "Open, Close and Axis" originated from inner Canon of Yellow Emperor. Original concept of "Open, Close and Axis" is a kind of description to door’s structure and functions. Inner Canon of Yellow Emperor developed it to the theory of Yang’s ascending, descending, exiting and entering. People’s Yang ascends, descends, exits and enters at body’s doors, and its working mechanism is "Open, Close and Axis". Everybody have two doors, one is yang door that is at body’s surface layer, another is yin door that is at body’s deep level. The two doors have its own "Open, Close and Axis". Taiyang is Open, yangming is Close and shaoyang is Axis at yang door. Taiyin is Open, jueyin is Close and shaoyin is Axis at yin door. The "Open, Close and Axis"at yang door and yin door is to be decided by yang’s ascending, descending, exiting and entering. It is because that yang is magistral between yin and yang. Yang is leader and yin is attendant. We discoursed that the functional characteristicof "Open, Close and Axis". Open is primary ascending and exiting. Close is primary descending and entering. Axis is the adjustor between Open and Close. "Open, Close and Axis" are uniform , integrated, interactive , compatible as a whole. The theory of "Open, Close and Axis" was developed and applied on the treatise on febrile and miscellaneous disease. We expatiate functional characteristics and the relationship among the three of "Open, Close and Axis". And then we explained the essential and its clinical manifestations of the theory of "Open, Close and Axis". Every people have two Axis. Shaoyang is Yang Axis and it responsible for Yang’s ascending, descending, exiting and entering at shallow layers. Shaoyin is Yin Axis and it responsible for Yang’s ascending, descending, exiting and entering at deep layer. Shaoyang and Shaoyin contacts closely and interact reciprocally in physiological effects. Shaoyang and Shaoyin influence mutual in pathological changes. In the treatise on febrile and miscellaneous disease, Xiaochaihutang is the primary prescription of Yang Axis’s dysfunction, Sinisan is the primary prescription of Yin Axis’s dysfunction. We expound the compositive principle and clinical applications of Xiaochaihutang and Sinisan. We bring forward a point of view: Chaihu is the best medicine of mediating Axis’s functions. According to 8 sides arguments, we made a conclusions that the occurrence and deterioration of diabetes is closely related to "Open, Close and Axis" dysfunction. According to academician Wangyongyan’s experiences in clinical and scientific research, his viewpoint about the key causes of diabetes is Axis’s dysfunction. Along with deferent diabetes periods, Axis’s dysfunction has deferent emphases. In early and metaphase period, the emphase is Shaoyang Axis’s dysfunction. In late stage, the emphase is Shaoyin Axis’s dysfunction. So, mediating Shaoyang Axis and Shaoyin Axis is the key of treatment. When the Axis’s dysfunction is improved, the diabetes sufferer’s sufferings are alleviated. Academician Wang invent the prescription of Chaihutiaoshutang. Chaihutiaoshutang is based on Xiaochaihutang and Sinisan and tie in academician Wang’s clinical experiences. By the clinical applications of Chaihutiaoshutang, we found that it has great curative effect.Clinical research: We evaluated on clinical curative effects and security of Chaihutiaoshutang for diabetes. In the research, 64 cases were allocated to treatment group (32 cases) and control group (32 cases) randomly. The treatment group were received a treatment on the base by adding or reducing drugs of Chaihutiaoshutang and metformin, the control group only received metformin. After 8 weeks, we observed the changes of fasting blood glucose, postprandial 2 hours blood glucose, glycosylated hemoglobin, blood routine examination, urine routine examination, stool routine examination, function examination of liver and kidney and Electro cardiograph, TCM symptom. By Ridit test and of the variance analysis repeated measure, we found that the effect of treatment group is better than control group’s at the level of fasting blood glucose, postprandial 2 hours blood glucose, TCM syndrome, diseases efficacy. There are no deference at glycosylated hemoglobin between the treatment group and control group. By comprehensive analysis, we believe that the effect of Chaihutiaoshutang and metformin is better than metformin;s at subjective and objective symptoms of patients. There are no side-effects in the clinical research. The study indicates that Chaihutiaoshutang based on the theory of "Open, Close and Axis" is effective and secure in treating diabetes.We made series of conclusions that the idea of Yang is leader and Yin is assistant is the key to traditional Chinese culture and TCM. The theory of "Open, Close and Axis" is the importent theory to research life and treat diseases. The key to diabetes is Axis ’s dysfunction. The symptoms of Shaoyang Axis dysfunction and Shaoyin Axis dysfunction is complicated and duality. The key construction to diabetes of Chaihutiaoshutang is point to Yang and Axis.We firstly introduced the theory of "Open, Close and Axis" into diabetes’s clinical research. We emphasized the role of Yang in traditional Chinese culture and TCM. Our research deepen the understanding to pathogenesis of diabetes, offer a new pathway for clinical therapy, blazed new trails and enrich the doctrines of pathogenesis and therapy.更多还原