【作者】 林士毅；

【导师】 李赛美；

【作者基本信息】 广州中医药大学 ， 中医临床基础， 2009， 博士

【摘要】 第一部分理论研究MS的提出把过去认为互不相关、彼此分割的疾病和代谢紊乱以IR为核心联系在一起,使人们对许多重要疾病的认识和处理发生了重大转变。目前MS发病在全球、特别是新兴经济国家呈迅速上升趋势,MS的防治形势已经非常严峻。MS的病因复杂,具有多病因致病的特点,是遗传易感、环境、生活方式等多种因素共同作用的结果。MS发病机制十分复杂,目前尚无法以单一因素圆满解释,目前比较公认的是IR为贯穿多种代谢相关疾病的主线,是这些疾病的共同病理生理基础。其次,炎症反应、神经内分泌异常因素与MS的关系也不可忽视。至今学术界对MS的诊断标准存在很大争议,2004年CDS关于MS的工作定义比较适合东方人群。MS涉及面广,临床表现复杂多样,通常起病缓慢,早期可无任何自觉症状,仅见于实验室检查的异常。鉴于当前MS流行情况,如何科学防治MS已成为了当前卫生行政部门和医务工作者面临的重大挑战。目前还没有统一的MS防治指南,现代医学以防止或延缓心脑血管疾病及2型糖尿病的发生和发展为主要目标。近几十年来,西医学在MS的基础研究和临床防治方面都取得了长足的进展,但还存在诸多疑难,还原、微观的研究方式本身存在误区,而且目前的防治方法还处于初级阶段。而中医学以其整体观的认识方式、“治未病”的医学思想、辨证论治的诊疗体系、丰富的养生学方法和天然、低毒、安全、价廉的中药,可以多成分、多环节、多靶点地综合调节人体机能,为MS的预防带来很多新思路、新方法,在防治MS中有着不可替代的明显的优势。MS中医并无相对应的病名,早在《内经》时代就留下了对MS认识的相关记载,后世医家也代有发挥,但没有形成专门论述,记载相对零散。近年来,中医药工作者对MS从各个角度进行了研究,涉及病因、病机、治法、复方、单药、针灸等方面,取得了一定的成果,但是至今尚未形成统一的认识。我们认为,只有建立了客观化、规范化的、能反映MS病机特点的辨证分型,才能有效地指导临床治疗,提高疗效。并充分利用现代科技成果,探讨各证候相对应的客观化指标,从而达到宏观辨证与微观辨证的统一。第二部分代谢综合征中医证候调查和病机研究目的研究分析广州地区成人MS中医证候类型,探讨MS病机特点和证候演变规律。同时,初步探索MS的六经辨证思路。方法通过横断面、前瞻性的调查研究方法,采用2004年CDS关于MS的工作定义和《中华人民共和国国家标准·中医临床诊疗术语证候部分》有关证候判定标准,确定纳入标准和排除标准,自制证候调查分析表,观察了MS患者518例。对四诊资料进行聚类分析,对每一类聚类分析所得的证型进行主成分分析,根据统计结果归纳MS的中医证型分布。同时,对每一例MS患者进行人工一般辨证,并加以频数分析,所得结果与聚类分析、主成分分析结果进行比较。此外,还对每一例患者进行六经辨证,并加以频数分析。结果(1)人工一般辨证频数分析结果:MS常多个证型相兼出现,具有3种及以上证型的患者占77.22%。从单一证候看,肝郁气滞、痰浊(湿)内盛、瘀血内阻较多,其次是气(阳)虚、湿热困阻、肾虚、气阴两虚、肝肾阴虚,再次是脾虚湿盛、肝阳上亢,而单独阴虚燥热、脾虚、阴阳两虚出现较少。从总体上看,MS的病机以痰湿内盛最多,气虚占第二位,其次是气滞、血瘀、阴虚、郁热、肾虚、脾虚等。(2)聚类分析和主成分分析结果:①肝阴不足、肝阳上亢证主要症状:烦躁、易怒、脉弦、咽干、两目干涩、颧红、发热。次要症状:口渴、五心烦热。②痰湿内阻、湿重于热、湿盛阳微证主要症状:头身困重、口中痰多、口黏不爽、咽部异物感、舌淡、舌胖大/齿痕、苔白腻(厚)、大便黏腻不爽。次要症状:脉滑、苔黄腻(厚)、脉沉、无食欲。③肝郁气滞、阳气亏虚证主要症状:闷闷不乐、紧张焦虑、健忘、易惊、自汗、气短、畏寒、肢冷、体虚易感、经前乳胀、心悸、神疲、乏力、小便多。次要症状:舌淡红、失眠、多梦、头晕、头痛、动则气短乏力尤甚、胸闷、苔裂纹/花剥、大便干、苔薄白、忧郁、面色苍白。④血瘀肾虚证主要症状:口唇色暗、舌暗红/瘀斑、面色晦暗、腰膝酸软。次要症状:性欲减退、齿松齿落、阳痿。⑤脾虚气滞兼有胃肠湿热伤阴证主要症状:脘痞、腹胀、嗳气、大便溏、舌瘦小、胁部不适、尿频尿急、脱发、苔薄黄。次要症状:耳鸣、苔黄、脉浮、工作压力大、盗汗、脉细、脉数、脉涩、少苔、口臭、苔白、纳少。(3)人工六经辨证频数分析结果:MS病变涉及六经,其中太阴病的发病率最高,占77.61%;其次是厥阴病(52.32%)、少阳病(48.07%)、少阴病(45.37%);阳明病也有不少的比例(31.08%);而太阳病最少,只有2.12%。大部分MS患者都是多经合病,其中两经合病(38.80%)、三经合病(31.47%)情况最为多见;五经同时发病很少,只有1.54%;没有见六经同时发病的情况。讨论(1)人工辨证可以灵活处理临床情况的复杂多变性,但是人工辨证不可避免地带有较强的主观性、经验性,而用高级统计的聚类分析和主成分分析进行研究,在完全没有先念的情况下作出前瞻性分析,大大提高了辨证的客观性和科学性。但是聚类方法分析的仅是简单的一对一的关系,在分析复杂问题时,可能会忽视系统多因素和非线性的特点。而且同一症状在中医学中可能属于不同证型,而聚类分析同一个症状只能归属一类,这就为证型的划分带来了不确定性。本论文两种研究方法所得结论基本一致,具有一定的可信度。(2)本论文在大样本调查MS中医证候的基础上,全面复习古今文献,深入探讨MS的中医病因病机和证候演化规律。认为肥食少动是MS的主要发病因素,而脏腑内虚、禀赋不足是其内应;脾胃损伤、脾气亏虚是MS发病的关键病机,痰湿气虚是临床最常见的MS证候特点;肝失疏泄既是MS发病的重要原因之一,又是MS发展变化的重要环节;而痰和瘀既是MS发生发展过程中的病理产物,又是新的致病因素,痰瘀互结、互为因果是MS的中医病理核心,贯穿着MS病程的始终;MS病机复杂,常气血阴阳之不足和郁、瘀、痰、湿、燥、热、毒等各方面互见,最终都造成肾元虚损,变证百出。总之,MS病位在脾肝肾,为本虚标实、虚实夹杂之证,以脾肾亏虚为本,痰瘀互结为标,肝失疏泄是其重要环节,虚损变证为最终病变结果。(3)本论文首次将六经辨证理论引入MS的辨证中,虽然在研究方法和水平上还存在诸多不足,但毕竟做了大胆的、有益的尝试,为今后的研究作了一定的铺垫。在MS中,太阴病最为多见,太阴虚寒湿符合岭南MS患者的病机特点。由于MS发病与精神因素密切相关,以及MS易寒易热、虚实夹杂的病机特点,与少阳、厥阴病紧密相连。同时,肾气在MS发病中的作用也不可小觑,而且久病及肾,特别是老年MS患者往往都具有肾虚因素,所以,少阴病在MS中也不在少数。“实则阳明,虚则太阴”,阳明病在早期MS患者中也为数不少。典型的太阳病在MS中并不多见,但由于六经是一个整体,他经疾患往往会影响太阳功能,特别是作为太阳底面的少阴,直接影响太阳的护卫功能。第三部分代谢综合征中医证型与微观指标相关研究目的探讨MS主要证候类型与微观医学检测指标存在的相关联系,为中医证候规范化研究和微观辨证奠定初步基础。方法从第二部分研究518例MS患者中,在常见的三个主要MS证型(痰湿气虚;气阴两虚、湿热内盛;痰瘀肾虚)中选出依从性较好的90例患者,每个证型各30例。另外,选择30例健康人作为对照组。纳入标准、排除标准、诊断标准同第二部分研究。分别检测FINS、2hINS、HbA1c、IAI、APN、LEP、FFA、TNF-α、IL-6等指标。结果和讨论(1) FINS水平在三个证型中基本都处于正常水平,表明在大部分MS患者中,FINS基本正常。更由于FINS正常值在1.9～23μIU/ml之间,本来相差较大,所以,FINS数值很难用来作为MS的辨证微观指标。2hINS水平三组都比正常值高,表明在MS患者中,胰岛素分泌代偿性增多,存在餐后高胰岛素血症,是IR的一个重要表现之一。而各组比较无显著性差异,可能也跟正常人INS数值就有很大差异有关,所以2hINS也难以用来作为MS的辨证微观指标。(2) HbA1c水平在痰湿气虚组基本处于正常范围,而在气阴两虚、湿热内盛组和痰瘀肾虚组则明显高于正常,其数值从高到低顺序为:痰瘀肾虚组＞气阴两虚、湿热内盛组＞痰湿气虚组。HbA1c能较为真实地反映患者的平均血糖水平,这一结果与MS中晚期T2DM的发病率明显上升一致。所以,HbA1c可以作为MS中医辨证分型的一个微观参考指标。(3) IAI数值从高到低顺序为:痰湿气虚组＞气阴两虚、湿热内盛组＞痰瘀肾虚组。反映了MS患者胰岛素敏感性从痰湿气虚型到气阴两虚、湿热内盛型,再到痰瘀肾虚型,逐渐降低,这也较为真实地反映了MS从病变早期到后期IR程度的加重。所以,IAI可以作为MS中医辨证分型参考的一个客观指标。(4)在气阴两虚、湿热内盛组和痰瘀肾虚组中,APN水平明显比痰湿气虚组以及健康对照组低,即:正常对照组≈痰湿气虚型＞气阴两虚、湿热内盛型≈痰瘀肾虚型。随着MS病情的发展,正气渐虚,邪气日益深入,具有保护性作用的APN也明显降低。APN可作为MS辨证论治的一个微观参考,它在一定程度上反映MS病程和“正气”的受损情况。(5) LEP水平在痰湿气虚组、气阴两虚湿热内盛组、健康对照组之间两两相比均无显著性差异,而痰瘀肾虚组与其他各组均有显著性差异,即LEP水平:痰瘀肾虚型＞气阴两虚、湿热内盛型≈痰湿气虚型≈正常对照组。随着MS病情的发展,IR程度越来越严重,LepR也随之加重,所以,在病程晚期LEP水平明显上升。所以,血清LEP水平也可作为MS辨证论治的一个微观参考。(6)在MS组中,血清FFA水平都比正常组高,差异具有显著性,说明FFA与MS密切相关。但在三个证型间FFA水平无显著性差异。这可能与三个证型都存在痰湿成分有关。从本课题的研究结果看,FFA难以成为MS的微观辨证指标。(7) TNF-α和IL-6是反映机体炎性反应的常用指标,本研究表明,TNF-α水平由高到低顺序为:痰湿气虚型≈气阴两虚、湿热内盛型＞痰瘀肾虚型＞正常对照组。而在IL-6方面,与健康组比较,只有气阴两虚、湿热内盛组有显著性差异。这种结果表明了MS的早、中期,特别是中期,炎症反应强烈。因此,TNF-α和IL-6可以作为MS微观辨证的一个参考指标,它反映了正邪抗争的激烈程度。更多还原

【Abstract】 Section 1 Theoretical Study of Metabolic SyndromeProposition of MS think each other independent in the past,disease and supersession disorder that cut apart each other regard IR as core their link together,make people know and deal with and take place the great change to a lot of important diseases.At present,the incidence of MS rise rapidly in the whole world,especially in developing economic country, the prevention and cure situation of MS has been already very severe.The pathogenic of MS is complicated,and have the characteristic of many causes resulted by many kinds of factors such as heredity,environment and life style.It is very complicated that MS has illness coming on in the mechanism,do not have a single factor that explain satisfactorily,the generally more acknowledged one is that IR is the thread run through many kinds of metabolic disorder at present,it is the physiological foundations of common pathology of these diseases.Secondly,the relation between reacting in inflammation,unusual factor of neural endocrine and MS can’t be ignored either.The diagnostic standard of MS existed greatly discussion,CDS works about MS in 2004 was defined and relatively suitable for the eastern.MS involves a wide range of knowledge,the clinical manifestation is complicated and various,get up disease to be slow usually,can have any subjective symptoms early,the only ones that checked in the laboratory.Seeing that present MS popular situation,how to prevent arid cure MS become a great challenge that the administrative department of the hygiene and medical personnel face scientifically.There is not the guide unified MS that prevent and cure at present,modern medical science regards preventing or delaying emergence and development of heart and brain blood vessel disease and 2 type diabetes as the main goal.In these decades nearly,modern medical science has made considerable progress in view of basic research and preventing and curing clinically of MS,but also there are a great deal of difficulties,the mistaken idea exists in reducing,micro research way,and the present prevention and cure method is also at primary stage.And TCM by way of its whole view’s understanding,"Cure before the disease" medical thought,whom dialectical theory manage make a diagnosis system,abundant health care study method and natural,low toxicity,safe,cheap traditional Chinese medicine,can many composition,many link,many target afford to order,bring a lot of new thought,new methods for the prevention of MS, there are irreplaceable obvious advantages in preventing and curing.There is no corresponding disease to MS in TCM,in "Huang Di Nei Jing" era leave for some records relevant where MS know,Doctors have some exertion in later age,but has not taken described systematiclly,has recorded relatively scattered.In recent years,TCM workers have carried on research from all angles to MS involving the cause of disease,ill machine,curing method,prescription,acupuncture and moxibustion,etc.But it has not formed unifying understanding yet.We considered that to set up objectify,standardized,can reflect MS pathogenesis differentiation type,could guide the clinical treatment effectively,and improve curative effect.And fully utilize the modern medical achievement,probe into the corresponding of the macro and micro Differentiation.Section2 Investigation to TCM Syndromes and study on pathogenesis of Metabolic SyndromeObjective:Research and analysis MS patients’ Syndromes of Guangzhou adults, probe into the pathogenesis and Syndromes regular pattern of developing of MS.Methods:Cross section,investigation research approach when it is prospective,it adopts define CDS about work of MS on the 2004 and "National standard in the People’s Republic of China·the part of Syndromes of TCM clinical diagnosis and therapy terms", and defines the standard of including and the standard of excluding,and make the analytical table of the investigation by myself,has observed 518 MS patients.Carries on classify analysis to the four methods of diagnosis materials,and carries on principal components analysis to every kind of results of classify analysis,and sum up the TCM Syndromes of MS according to the statistics.Meanwhile,carry on artificially Differentiation on every MS patients,and analyzes the result compared with cluster’s analysis’.Meanwhile,pass to every patient with Liujing Differentiation and analyzed with Frequency Analysis. Results:(1)The result of the frequence analysis of syndrome differentiation:It is often concurrently appeared a lot of Syndromes on MS patients,the patient with 3 kinds of Syndromes accounts for 77.22%.As a whole,accumulation of phlegm occupies the first place of DM Pathogenesis,and the deficiency of vital energy occupies the second place, and stagnation of the circulation of vital energy,blood silt,deficiency of Yin,strongly fragrant and hot,suffers from a deficiency of the kidney,the spleen is empty in following.(2) The result of artificially Liujing Differentiation:MS pathological change involves Liujing,among them the morbidity of the Taiyin disease is the highest,accounts for 77.61%; and the Jueyin disease(52.32%),the Shaoyang(48.07%),the Shaoyin disease(45.37%) secondly;and the Yangming disease have many proportion too(31.08%);And the Taiyang disease only 2.12%.Most MS patient has More than two Jing disease.(3)The results classify analysis and principal components analysis:deficiency of liver-yin,hyperactivity of liver-yang syndrome;accumulation of phlegm,damp more than heat,damp flourishing and Yang decline syndrome;Qi stagnation of the liver,the deficiency of Yang-qi syndrome;blood stasis and kidney deficiency syndrome;spleen deficiency and stagnation of Qi and damp-heat impairment Yin syndrome.Discuss:(1)The artificial Differentiation can deal clinical situation flexibly,but there are unavoidably stronger subjectivity,experience in it,but with classify analysis and principal components analysis,it can make prospective analysis the results in case of not personal-conception first at all,has improved the objectivity and science of Differentiation greatly.But what classify analysis is analyzed is only a simple one-to-one relation,while analyzing the complicated problem,it may ignore the characteristic with multifactor and non-linear relationship.The resulting conclusion of two kinds of research approaches of this thesis is basically identical,have certain credibilities.(2)This thesis considered disease location of MS is on the spleen,kidney and liver,the syndromes is the deficiency of essence and excess of Surface,and inclusion deficiency and excess.The deficiency of kidney and spleen is the essence,and accumulation of phlegm and blood stasis is the Surface,the disorder of Liver to maintain free flow of Qi is the important link,and changing into the weakness syndrome is the final result.(3) This Thesis deal MS Differentiation with Liujing Differentiation for the first time. Though there are many shortage,the research has done the bold,beneficial attempt to MS prevention and cure.Among MS,the Taiyin disease is the largest,it accord with the disease machine characteristic of the Lingnan patients.Because it is closely related to spiritual factor,and the disease machine characteristic is apt to cold and hot,and inclusive with Deficiency and excess Syndromes,so MS linked to the Shaoyang disease and the Jueyin disease closely.Meanwhile,the function of kidney-Qi can’t be neglected,and long disease will injure the kidney,especially old MS patients often have the factor of the kidney deficiency,so the Shaoyin disease are not small number in MS.the Yangming disease comes up to a large number among MS patient too.But Taiyang sun disease is actually rare in MS.Section3 Study on the correlation with TCM Syndromes of Metabolic Syndrome and micro-IndicatorsObjective:Research on the correlation with the mainly TCM Syndromes of Metabolic Syndrome and micro-indicators of modern medical,in order to establish the initial foundation of the Standardization Study of TCM Syndromes and Micro-differentiation of MS.Methods:Based on the second Section research,common three main MS syndrome types(accumulation of phlegm and deficiency of Qi syndrome;deficiency of Qi-Yin, damp-heat inside flourishing syndrome;accumulation of phlegm and blood stasis and kidney deficiency syndrome),selected 90 MS patients,and 30 for every group.In addition, choose 30 healthy persons as the control group.Then measure the indicators such as FINS, 2hINS,HbA1c,IAI,ADP,LEP,FFA,TNF-α,IL-6,etc.Resuits and Discuss:(1)FINS level in normal level basically in three syndrome types. Because of the normal value of FINS is 1.9～23μIU/ml,the discrepancy is great,so it is difficult to regard FINS as a micro-Indicators of MS TCM Syndromes.2hINS level,the three groups of MS are on the high side than normal.It indicats that insulin is secreted the compensating and increased,there is high insulin blood level after the meal.It is one representation of IR.But it is difficult to regard as a micro-Indicators of MS TCM Syndromes too.(2)HbA1c is basically in the normal level in the accumulation of phlegm and deficiency of Qi syndrome group.But it is the majority higher than normal in the deficiency of Qi-Yin,damp-heat inside flourishing syndrome group and the accumulation of phlegm and blood stasis and kidney deficiency syndrome group.HbA1c can comparatively reflect the patient’s average blood glucose level truly.So it can be regarded as a micro-Indicators of MS TCM Syndromes.(3)From the accumulation of phlegm and deficiency of Qi syndrome group to the deficiency of Qi-Yin and damp-heat inside flourishing syndrome group,to the accumulation of phlegm and blood stasis and kidney deficiency syndrome group,the numerical value of IAI is reduced gradually,has reflected comparatively truly that IR intensity is aggravated from is early to later stage of MS.IAI can be seen as an objective Indicators of Micro-differentiation of MS.(4)Among the deficiency of Qi-Yin,damp-heat inside flourishing syndrome group and the accumulation of phlegm and blood stasis and kidney deficiency syndrome group patients,the APN level is lower than the normal group and the accumulation of phlegm and deficiency of Qi syndrome group patients.Its level from high to low order is:the normal control group≈the accumulation of phlegm and deficiency of Qi syndrome group>the deficiency of Qi-Yin,damp-heat inside flourishing syndrome group≈the accumulation of phlegm and blood stasis and kidney deficiency syndrome group.APN can be seen as an objective Indicators of Micro-differentiation of MS.(5)In the accumulation of phlegm and blood stasis and kidney deficiency syndrome group,the serum level of LEP is higher than the other groups.With the development of MS condition,IR intensity is more and more serious,thereupon LepR aggravates too,so the serum level of LEP obviously increases in later course of MS.LEP can be seen as a referenced Indicators of Micro-differentiation of MS.(6)In MS group,the serum levels of FFA is higher than the normal group,the difference is significance,prove FFA is closely related to MS.But FFA level does not have significance difference among three syndrome types.This maybe relates to the fact that three syndrome types all have the phlegm Factor.By the look of result of this subject,FFA is difficult to become the Micro-differentiation Indicators of MS.(7)TNF-αand IL-6 are the Indicators that reflect the inflammation reaction of the organism.This research indicates,the change of TNF-αlevel is:the accumulation of phlegm and deficiency of Qi syndrome group≈the deficiency of Qi-Yin,damp-heat inside flourishing syndrome group>the accumulation of phlegm and blood stasis and kidney deficiency syndrome group≈the normal control group.But among three syndrome types groups,the IL-6 level only the deficiency of Qi-Yin,damp-heat inside flourishing syndrome group is obviously higher than the normal control group.TNF-αand IL-6 can be seen as a referenced Indicators of Micro-differentiation of MS,it reflects the Intensity of fighting with Vital-Qi and pathogens.更多还原