【作者】 罗礼达；

【导师】 朱章志；

【作者基本信息】 广州中医药大学 ， 中医临床基础， 2009， 博士

【摘要】 研究背景:近年来,中医药在治疗2型糖尿病及其并发症方面逐步体现出独特的优势,特别是中药复方的多靶点作用,整体调节机体免疫,达到“扶正以祛邪,祛邪不伤正”的目的。随着人们生活水平的提高及生活方式的改变,2型糖尿病的发病率越来越高,现已成为继肿瘤及心血管疾病之后第三位导致人类死亡的疾病。中医药对于本病的临床治疗现多采用辨病与辨证相结合的方法,多以养阴清热、益气养阴、清热生津、健脾化湿及活血化瘀等为主,其作用机理与改善胰岛素抵抗、调节脂糖代谢紊乱及减少炎症反应等有关。上述研究加深了对运用中医药治疗2型糖尿病的认识,但还存在不少亟待解决的问题。本病的发生与体质、环境、生活习惯等多种因素相关,不同治法在疾病的不同阶段发挥作用,如何在治法研究中体现“辨证”的思路,有待进一步探讨。研究目的:临床中发现2型糖尿病患者存在明显的正气不足、阳气虚弱的特点,从六经辨证的观点来看,以三阴病本,兼夹以少阳病为标,三阴病又以太阴病为统。本研究观察从三阴病入手以温脏扶正祛邪法组方治疗2型糖尿病的临床疗效、对中医症候的改善作用、对胰岛素抵抗的改善作用、对糖脂代谢紊乱的纠正作用及对患者T淋巴细胞免疫功能的调节作用,并初步探讨其作用机理。研究方法:1.文献研究将目前中医药对2型糖尿病的研究现状进行综述,从病名、病因、病机、辨证分型、治疗等角度进行论述,提出了目前中医学认识2型糖尿病仍以阴虚燥热、气阴两虚论为主,治疗上多从清热养阴、益气养阴、健脾活血等为主,从《伤寒论》六经辨证及阳气亏虚角度论治者鲜见报道。2.临床研究将2007年3月至2009年4月广州中医药大学第一附属医院内分泌专科门诊符合西医2型糖尿病诊断标准且中医辨证符合三阴病虚寒证患者73例分为治疗组38例和对照组35例,两组均采取相同的基础治疗,包括糖尿病教育、糖尿病饮食、适度运动等。对照组在基础治疗的基础上加西药盐酸二甲双胍片（0.50g,po,bid,饭后）及达美康（格列齐特片,80mg,po,bid,饭前）治疗,治疗组在对照组的基础上加用温脏扶正祛邪中药复方,水煎服,每日1剂,以1个月为一个疗程。观察治疗前后2型糖尿病临床疗效、中医症候疗效、中医症候积分变化,检测空腹血糖、餐后2小时血糖、空腹胰岛素、TC、TG、HDL-C、LDL-C、CD4+、CD8+、CD4+/CD8+,计算胰岛素敏感指数、胰岛素抵抗指数等并进行比较。研究结果:1.两组在性别、年龄、病程、中医症候积分、FBG、P₂Hbg、血脂四项、T淋巴细胞免疫功能等方面比较无明显差异（P＞0.05）,具有可比性。2.临床观察结果显示治疗组总有效率为84.3%,明显优于对照组的65.7%（P＜0.05）,表明合用温脏扶正祛邪中药复方可以增强西药对T2DM的临床疗效;治疗组中医症候总有效率100.0%,明显优于对照组74.3%,说明中药在改善症状方面优于单纯西药;两组均能明显减轻患者中医症状积分（P＜0.05）,差值比较治疗组优于对照组（P＜0.05）,说明合用温脏扶正祛邪中药复方后可更明显改善患者症状,提高生活质量;两组均能明显降低患者的FBG和P₂hBG（P＜0.01）,但治疗后两组组间比较无显着差异（P＞0.05）,表明温脏扶正祛邪中药复方并非通过提高降糖效果来实现改善中医症状的作用;两组均能使空腹胰岛素、胰岛素抵抗指数明显降低,胰岛素敏感指数明显升高,与治疗前比较,有显着性差异（P＜0.05或P＜0.01）,两组组间比较虽然无明显差异（P＞0.05）,治疗组改善胰岛素抵抗指数及胰岛素敏感指数的作用要优于对照组,说明中药可能具有一定的改善胰岛素抵抗作用;两组治疗后TC、TG、及LDL-C均显着下降,HDL-C升高,与治疗前比较,差异有显着性意义（P＜0.05）,治疗后两组比较,治疗组TC、TG及LDL-C的改善均优于对照组（P＜0.05）,HDL-C较对照组亦有升高,但无统计学意义（P＞0.05）,表明中药具有一定的调节血脂紊乱作用;两组治疗后CD4+、CD8+、及CD4+/CD8+均升高,其中对照组与治疗前比较,无显着性差异（P＞0.05）,治疗组与治疗前比较有显着性意义（P＜0.05）,表明温脏扶正祛邪中药复方对机体的T淋巴细胞免疫功能有一定的调节作用。3.患者在服用温脏扶正祛邪中药复方过程中未出现任何毒副作用。结论:1.阳虚可以致消,正虚也可以致消;三阴病阳（气）亏虚伴少阳枢机不利是2型糖尿病的发病基础,在此基础上产生的寒湿痰瘀等是其重要的病理因素。针对2型糖尿病三阴阳（气）亏虚,枢机不利,邪毒内阻的特点,以温脏扶正祛邪法温三阴之脏、扶助正气、畅少阳枢机,以祛邪外出为T2DM的基本治法。2.温脏扶正祛邪法中药复方可辅助西药提高三阴病虚寒证2型糖尿病临床疗效,减轻其中医临床症状,协助降低血糖,改善胰岛素抵抗并纠正脂代谢紊乱。3.T2DM患者存在明显的T淋巴细胞功能降低,T淋巴细胞免疫功能与机体正气强弱关系密切,温脏扶正祛邪法中药复方能提高T2DM患者血清CD4+、CD8+及CD4+/CD8+的表达,改善2型糖尿病患者机体T淋巴细胞免疫功能,增强机体免疫力,其治疗2型糖尿病的机理并不是通过单纯降低血糖,而是通过神经-内分泌-免疫调节网络对机体进行整体调节,从而达到邪去正安的目的。更多还原

【Abstract】 Background:In recent years,Chinese medicine has gradually reflected a unique advantage in the treatment of type 2 diabetes mellitus（T2DM） and its complications.The role of multi-targets owned by TCM can regulate the body immune function so as to achieve the goal of ’reinforce the healthy qi to eliminate the pathogenic factors,eliminate the pathogenic factors without the healthy qi damage’.With the improvement of living standards and lifestyle changes,the incidence rate of Type 2 diabetes is getting higher and higher. It has become the third disease which result in death following after the tumor and cardiovascular diseases.For the treatment of this disease,most Chinese medicine doctors use the combination method of syndrome differentiation and disease differentiation.The common therapeutic methods include inriching yin and clearing heat,tonifying qi and inriching yin,clearing heat and engendering fluid,fortifying the spleen and resolving dampness,activating blood and resolving stasis,etc.The mechanisms are related to improving insulin resistance,adjusting the disorders of blood glucose and lipid, reducing inflammation etc.The research mentioned above deepened our knowledge of TCM treatment on T2DM.Nevertheless,there are still a lot of problems that need to be settled urgently in this field.Many factors such as constitution, environment and living habit are related to T2DM occurrence.Different treatments work at different stages of this disease.How to embody the ’syndorme differentiation’ of the treatment demands further studied.Objective:The characteristic of healthy qi and yang qi deficiency is found in clinical on T2DM patients.From the six-meridian syndrome differentiation point of view T2DM occurs based on san-yin disease which complicated by lesser yang disease and controlled by greater disease.Based on the treatment of ’warming viscera,reinforce healthy qi and eliminate the pathogenic factors’ a decoction named WenZangFuZhengquxie（WZFZ） was produced.This research is to observe the effect of WZFZ in the T2DM clinical,the improving symptoms of TCM,the improving insulin resistance,the adjusting blood blucose and lipid,the regulation of T lymphocytes immune function and primarily probe its mechanism.Methods:1.The present status of TCM study on T2DM is reviewed in literature research.At present,yin deficiency with internal heat and deficiency of qi and yin are the most two common mechanisms of T2DM in TCM point.Under these theories influence clinical doctors get used to the treatment methods like inriching yin and clearing heat,tonifying qi and inriching yin,fortifying the spleen and activiting blood,etc.But it is rarely in the study based on Treatise on Cold Damage Diseases and six-meridian syndrome differentiation.2.73 T2DM patients who were diagnosed with deficiency cold syndrome blongs to san-yin disease were randomly divided in to two groups:treating group（n=38） and control group（n=35）.All those patients were selected from the endocrinology clinic of the First affiliated hospital of Guangzhou university of Chinese Medicine during March 2007 to March 2009.2 groups were giver the same basal treatment including education course for diabetes,diabetic diet and moderate exercise.Patients in the control group attended to metformin hydrochloride（0.50g,po,bid,after meals） and gliclazide（80mg,po,bid, before meals）.And to those in the treating group,WZFZ therapy was given additionally,one dose taken in twice a day.After 1 month’ s treatment,the curative effect and Chinese medical syndromes were observed.Moreover,fasting blood glucose（FBG）,post-prandial 2-hour blood glucose（P₂hBG）,blood lipid, fasting insulin（FINS）,insulin resistance index（IRI）,insulin sensitivity index（ISI）,CD4+,CD8+ and CD4+/CD8+ were measured and compared before and after treatment. Results:1.The difference among sex,age,TCM syndromes,FBG,P₂Hbg,blood lipid and T lymphocytes immune function were not signification between treating group and control group（P＞0.05）.2.Based on controlling the blood glucose availability,the total ratio of effective of treating group was 84.3%,control group was 65.7%.Compared with two groups,treating group was obviously excel to control group（P＜0.05）.In the total effective ratio of TCM syndrome,the treating group achieved 100.0%significantly higher than the control group 74.3%（P＜0.05）. Both groups had a obviously decrease in the syndrome scores（P＜0.05）,while in the comparison of difference treating group was superiorer to control group （P＜0.05）.FBG and P₂hBG lowered in both groups（P＜0.01）,but no difference was found between the treating group and control group（P＞0.05）.Both groups can decrease the FINS and IRI as well as increase the ISI（P＜0.05）.Also, no difference was found between groups（P＞0.05）.Both groups worked good in blood lipid regulation with a significant difference compared with before treatment（P＜0.05）.Compared with two groups,treating group was superior to control group in decreasing TC,TG,and LDL-C（P＜0.05）,but not significant in increasing HDL-C（P＞0.05）.In the aspect of adjusting T lymphocytes immune function,compared with their levels before treatment separately,treating group made a better effect in increasing the levels of CD4+,CD8+ and CD4+/CD8+ （P＜0.05）,however,the control group not（P＞0.05）.3.There are no toxicity and side-effect in tow groups.Conclusions:1.Yang qi of human body is deficient easy,and the deficiency of yang qi can also incur to diabetes.The same situation occurs when the healthy qi is deficient.The yang qi deficiency of san-yin disease complicated by the lesser yang disease is the main mechanism of T2DM.All the pathogenic factors include cold,dampness,phlegm and static blood are produced on this basis. According to this characteristic,a treatment method named ’warming viscera, reinforce healthy qi and eliminate the pathogenic factors’ is established. And this method is used to warm the viscera of san-yin,reinforce the healthy qi,harmonize lesser yang and eliminate the pathogenic factors.2.The WZFZ can increase the clinical efficacy of T2DM,decrease the TCM syndromes,lower FBG and P₂hBG,improve insulin resistance and injust the disorders of blood lipid.3.Diabetic patients have a significant lower T-lymphocyte function which closely related with the healthy qi of body than normal person.WZFZ can increase the levels of CD4+,CD8+ and CD4+/CD8+ to improve the T lymphocyte function of diabetic patients and enhance the immunological function of body. The therapeutic mechanism for T2DM is not depend on the controlling blood glucose availability,but is probably pathway of relating to regulate the immunological function.It can regulate organism all round through neuro-endocrinc-immunomodulation network of the whole body.更多还原