【作者】 毕小丽；

【导师】 彭万年；

【作者基本信息】 广州中医药大学 ， 中医临床基础， 2009， 博士

【摘要】 1.研究背景糖尿病合并冠心病的发病率不断增加,已成为糖尿病患者致死致残的主要原因,这不仅对患者的生活质量及生命构成严重的威胁,也给社会带来了巨大的经济压力。因其严重的临床表现以及与糖尿病患者死亡的高度相关性,已经成为当今医学界的研究热点。国内外学者对糖尿病合并冠心病的研究十分重视,从不同角度、采用不同方法进行观察研究,但迄今为止,该病的病因病机尚未完全阐明,在其临床治疗方面仍以对症治疗为主。因此,探寻该病有效的防治方案已经成为当务之急。中医药在治疗糖尿病及其并发症方面有悠久的历史和丰富的经验,特别是在辨证论治基础上的灵活处方用药是中医药的优势所在,因此,寻求糖尿病合并冠心病的中医药有效治疗方法显得尤为迫切。2.研究目的验证益气温阳通痹法(桂枝甘草汤合瓜蒌薤白半夏汤加减)治疗糖尿病合并冠心病的疗效及相关中医药优势,探讨糖尿病合并冠心病的中医病因病机及证治规律。通过治疗前后检测指标的客观变化情况,揭示其作用机理。旨在探索防治糖尿病合并冠心病的有效方药,从而为中医药治疗糖尿病合并冠心病提供新的思路与方法。3.研究内容与方法主要包括理论和文献研究及临床研究两个部分。3.1理论和文献研究部分该部分包括三个方面的内容。首先,回顾了近年来现代医学对糖尿病合并冠心病的研究进展,主要从糖尿病合并冠心病的流行病学研究、临床特点、发病机理、实验室检查、治疗等方面进行总结。其次,重点介绍了血清胱抑素C的生物学特性、测定方法及其与心血管疾病的关系。最后,着重介绍了糖尿病合并冠心病的中医药研究进展,包括中医病名的认识、病因病机、实验研究、辨证施治、中成药治疗、单味药研究等方面。3.2临床研究部分该部分观察了益气温阳通痹法治疗糖尿病合并冠心病的临床疗效,采用随机对照临床试验设计方法,纳入统计的合格受试对象有88例,其中治疗组45例,对照组43例。对照组给予包括教育心理调整、饮食控制、适当运动、控制血糖和对症处理等在内的基础治疗,治疗组在对照组的基础上,加用益气温阳通痹中药汤剂进行辨证分型治疗,中药每日1剂,水煎约200ml,分两次口服。两组均治疗观察8周。重点观察中医临床症状、血清胱抑素C、尿微量白蛋白、空腹血糖、餐后2小时血糖、糖化血红蛋白、血脂、心电图、超声心动图等指标。4.结果4.1两组临床总疗效的比较,治疗组显效11例,有效18例,无效16例,总有效率为64.4%,对照组显效9例,有效13例,无效21例,总有效率为51.1%,治疗组的总有效率高于对照组,但经统计学处理,差异无统计学意义(P＞0.05),还不能认为两组总疗效有差别,两组疗效相当。4.2两组中医证候疗效的比较,治疗组临床痊愈5例,显效11例,有效25例,无效4例,总有效率为91.1%,对照组临床痊愈2例,显效8例,有效15例,无效18例,总有效率为58.1%,治疗组中医证候疗效优于对照组(P＜0.01)。4.3两组患者中医症状积分的比较,与本组治疗前相比,两组治疗后症状积分下降有统计学意义(P＜0.01),可以认为两组治疗后的中医症状积分降低。两组治疗后症状积分下降差值相比较,差异有统计学意义(P＜0.01),可以认为两组不同治疗方法对中医症状积分的降低效果不同,治疗组降低效果较好。4.4治疗组治疗前后的FPG值相比,差异有统计学意义(P＜0.01),对照组治疗前后的FPG值相比,差异无统计学意义(P＞0.05)。两组治疗后FPG下降差值的比较,差异有统计学意义(P＜0.01),可以认为两组不同的治疗方法对FPG的降低效果不同,治疗组降低FPG效果较好。治疗组治疗前后的2hPG值相比,差异有统计学意义(P＜0.01),对照组治疗前后的2hPG值相比,差异无统计学意义(P＞0.05)。而两组治疗后2hPG下降差值的比较,差异有统计学意义(P＜0.05),可以认为两组不同治疗方法对2hPG的降低效果不同,治疗组降低2hPG效果较好。两组治疗后的HbAlc均有所下降,可以认为两组治疗后的HbAlc降低(P＜0.05)。而两组治疗后HbAlc下降差值的比较,差异无统计学意义(P＞0.05),还不能认为两组不同的治疗方法对HbAlc的降低效果不同,两组疗效相当。4.5两组治疗后的mALB值均有所下降,可以认为两组治疗后的mALB降低(P＜0.05)。而两组治疗后mALB下降差值的比较,差异无统计学意义(P＞0.05),还不能认为两组不同的治疗方法对mALB的降低效果不同。4.6两组治疗后的Cys C值均有所下降,与本组治疗前相比,经统计学处理,P＜0.01,差异有统计学意义,可以认为两组治疗后的Cys C降低。而两组治疗后Cys C下降差值的比较,经统计学处理,P＜0.05,差异有统计学意义,可以认为两组不同的治疗方法对Cys C的降低效果不同,治疗组降低Cys C效果较好。4.7两组治疗后的CHOL、TG、LDL-C水平有所下降,而HDL-C水平则有上升趋势。与本组治疗前相比,差异有统计学意义(P＜0.05),可以认为两组在治疗之后的CHOL、TG、LDL-C值降低,HDL-C值升高。两组治疗前后CHOL、HDL-C差值的比较,差异无统计学意义(P＞0.05),还不能认为两组不同的治疗方法对CHOL的降低、HDL-C的升高效果有所不同。而治疗后TG、LDL-C的组间比较,差异有统计学意义(P＜0.05),可以认为两组不同的治疗方法对TG、LDL-C的降低效果不同,治疗组降低效果较好。4.8两组心电图疗效的比较,治疗组心电图显效16例,有效19例,无效10例,总有效率为77.8%,对照组显效10例,有效14例,无效19例,总有效率为55.8%,治疗组心电图疗效优于对照组(P＜0.05)。4.9两组在治疗期间均未发生不良反应,治疗前后的血分析(WBC、HGB、RBC、PLT)、肝功能(ALT、AST)、肾功能(BUN、CREA)的比较,差异无统计学意义(P＞0.05)。5.结论5.1糖尿病合并冠心病相当于中医学“消渴”、“胸痹心痛”等范畴,可称为“消渴病心病”,其病因是消渴病迁延不愈、日久生变而成,其发病与年老体虚、劳倦内伤、饮食不节、情志失调、久病不愈等因素有关。其病位在心,与肺、脾、肝、肾密切相关。病性属本虚标实、虚实夹杂。5.2气阴两虚是糖尿病合并冠心病的发病基础,在此基础上,演变为气血阴阳的亏虚,其中,心气虚、心阳虚是糖尿病合并冠心病的病机关键,脾肾亏虚是糖尿病合并冠心病的中心环节,痰浊、血瘀贯穿糖尿病合并冠心病的始终。5.3治疗上应标本兼顾,扶正祛邪。本虚宜补,应权衡气血阴阳之不足,调阴阳补气血,调整脏腑之偏衰,尤应重视补益心气、温通心阳。标实宜泻,针对气滞、血瘀、寒凝、痰浊而理气、活血、温通、化痰,尤重活血通络治法。特别强调益气温阳通痹的治疗方法。5.4临床研究证实了益气温阳通痹法可明显缓解糖尿病合并冠心病患者胸闷胸痛等临床症状,提高患者生活质量,能够降低空腹血糖及餐后2小时血糖,改善心肌缺血状态,能够纠正脂代谢紊乱,降低血清胱抑素C水平。5.5其作用机制可能与调节糖代谢、纠正脂代谢紊乱、改善心肌缺血、保护心肾功能等有关。5.6治疗组可以降低血清Cys C水平,鉴于血清Cys C在一定程度上能够反映冠心病患者的病情程度及心脏功能,对冠心病患者将来继发心血管事件及在其死亡率方面有独立的预测价值,血清Cys C的检测可作为动态观察指标,它的测定能够为临床医生提供参考,提醒临床医生及时选择更加合适的治疗方法,具有临床实用价值。血清Cys C与糖尿病合并冠心病的关系还需要更深入的研究,其作用机制有待于进一步探讨。临床上,应结合其它指标综合分析,从而对糖尿病合并冠心病的发展、预后做出客观评价。5.7研究过程中,未发现任何不良反应,临床使用安全。本研究初步显示出中医药在缓解临床症状、提高生活质量、改善实验室检测指标等方面有较大的优势。益气温阳通痹法治疗糖尿病合并冠心病,切中病机,临床疗效确切,安全性好,值得进一步推广。更多还原

【Abstract】 1 BackgroundWith the incidence of DM with CHD increased,it has become the main reason for disability or death in diabetic patients;it will not only affect the quality of life for patients and pose a serious threat to life,but also create an enormous financial burden for the society.Prevention and treatment of DM with CHD has become the focus of research in recent years.Domestic and foreign scholars attach great importance to this problem and have carried out a number of studies on DM with CHD.So far,however,the pathogeny has not yet been fully clarified;its clinical treatment is still mainly symptomatic treatment.Therefore,the search for effective disease control programs has become a top priority.TCM in the treatment of diabetes and its complications have a long history and rich experience,especially in the treatment of flexibility based on the prescription medication is the advantages of TCM,Therefore,the search for DM with CHD in Chinese medicine effective treatment methods will become more necessary.2 ObjectivesThe objectives of this clinical observation are to judge the curative effect of Replenishing Qi,Warming Yang,Resolving Stagnation Therapy(Ramuli Cinnamomi and Glycyrrhizae Decoction combined Gualou Xiebai Decoction) on DM with CHD according to the curative standard and verify the advantages of TCM; to explore its etiology and pathogenesis and probe into treatment of the law; to reveal its mechanism according to the changes of clinical symptoms and laboratory indexes before and after treatment;to search for the effective prescriptions and provide new ideas and methods for the prevention and treatment of DM with CHD.3 Contents and methods of studyThis paper consists of two parts,which are summaries of documents and a clinical observation.3.1 Theoretical and document researchTheoretical and document research includes the three parts.First of all, we review the modern medicine studies on DM with CHD in recent years,including epidemiological study,clinical manifestation,etiopathogenesis,laboratory examination and treatment,etc.Secondly,we focus on the biological characteristics of serum cystatin C,its determination and the relationship between Cys C and cardiovascular disease.Finally,introduce the traditional Chinese medical research progress about MD with CHD,including awareness of the Names of Disease,etiology and pathogenesis,experimental research, treatment based on syndrome differentiation,Chinese formulated products treatment,single drug research.3.2 Clinical observationThe clinical study observes the clinical effect of Replenishing Qi, Warming Yang,and Resolving Stagnation Therapy on treating DM with CHD.88 patients conforming to the diagnostic criterion were randomly divided into two groups,which are treatment group(45 patients) and control group(43 patients).Education and psychological adjustment,alimentary control,proper exercise,control blood glucose and symptomatic therapy were given to the control group,on the basis of suitable remedy,Chinese medicine was applied in the treatment group,which has the function of Replenishing Qi,Warming Yang,Resolving Stagnation.Take a dose twice a day.Two groups were treated for 8 weeks.The clinical symptoms,serum cystatin C,mALB,FPG,2hPG, glycosylated hemoglobin,blood lipid,electrocardiogram and ultrasonic cardiogram were observed.4 Results4.1 The result of clinical comprehensive efficacy:In treatment group, among the 45 cases,11 cases were markedly effective,18 cases were effective and 16 cases were ineffective,the total effective rate was 64.4%.As for the control group,among the 43 cases,9 cases were markedly effective,13 cases were effective and 21 cases were ineffective,the total effective rate was 51.1%.The total effective rate in treatment group is higher than in control group.By statistics,no-significant difference was revealed(P＞0.05).4.2 The result of Chinese medicine syndromes:In treatment group,among the 45 cases,5 cases were cured,11 cases were markedly effective,25 cases were effective and 4 cases were ineffective,the total effective rate was 91.1%.As for the control group,among the 43 cases,2 caseswerecured,8cases were markedly effective,15 cases were effective and 18 cases were ineffective, the total effective rate was 58.1%.The treatment group was superior to the control group in Chinese medicine syndromes efficacy(P＜0.01).4.3 Scores of syndrome of TCM:Compaired with pre-post treatment,scores of syndrome of TCM descented obviously(P＜0.01).It is clear that the scores of syndrome of TCM in treatment group and control group after treatment were significantly lower than that before treatment.Comparing the scores of syndrome of TCM between the two groups,there was significant difference between treatment group and control group(P＜0.01).4.4 Compaired with pre-post treatment,fasting plasma glucose descented in treatment group(P＜0.01).There was no significant difference in control troup before and after treatment(P＞0.05).Comparing the level of FPG between the two groups,there was significant difference(P＜0.01).The treatment group was superior to the control group in decreasing FPG.Compaired with pre-post treatment,two-hour postprandial plasma glucose descented in treatment group(P＜0.01).There was no significant difference in control troup before and after treatment(P＞0.05).Comparing the level of 2hPGbetweenthe two groups,there was significant difference(P＜0.05). The treatment group was superior to the control group in decreasing 2hPG.After treatment HbAlc was decreased in treatment group and control group. Compaired with pre-post treatment,the difference was statistically significant(P＜0.05).Comparing the level of HbAlc between the two groups, there was no significant difference(P＞0.05).4.5 After treatment mALB was decreased in treatment group and control group. Compaired with pre-post treatment,the difference was statistically significant(P＜0.05).Comparing the level of mALBbetweenthe two groups, there was no significant difference(P＞0.05).4.6 After treatment serum Cys C was decreased in treatment group and control group.Compaired with pre-post treatment,the difference was statistically significant(P＜0.01).Comparing the level of serum Cys C between the two groups,there was significant difference(P＜0.05).The treatment group was superior to the control group in decreasing serum Cys C.4.7 After treatment CHOL,TG and LDL-C were decreased in treatment group and control group.At the same time,HDL-C was increased.Compaired with pre-post treatment,the difference was statistically significant(P＜0.05). Comparing the levels of CHOL and HDL-C between the two groups,there were no significant differences(P＞0.05).Comparing the levels of TG and LDL-C between the two groups,there were significant differences(P＜0.05).The treatment group was superior to the control group in decreasing TG and LDL-C.4.8 The result of electrocardiogram efficiencies:In treatment group, among the 45 cases,16 cases were markedly effective,19 cases were effective and 10 cases were ineffective,the total effective rate was 77.8%.As for the control group,among the 43 cases,10 cases were markedly effective,14 cases were effective and 19 cases were ineffective,the total effective rate was 55.8%.The treatment group was superior to the control group in electrocardiogram efficiencies(P＜0.05).4.9 During treatment the two groups had no obvious side effects.Compaired with pre-post treatment,there were no significant differences in hemanalysis, hepatic funtion or renal function(P＞0.05).5 Conclusions5.1DM with CHD is nearly equivalent to "wasting-thirst" and "chest pain" according to TCM term,which can be referred to as the "Heart of Diabetes" It always changes from a long period of time.Some factors are relevant to the development of DM with CHD,such as old age and weakness, overstrain and internal injuries,improper diet,emotional maladjustment, obstinate disease,etc.Its disease-bit heart,lung,spleen,liver and kidney are closely related,which is syndrome of deficiency Ben and excessive Biao, deficiency and excess interlace each other.5.2 Qi and Yin Deficiency is the foundation of DM with CHD which makes deficiency of yin,yang,qi,blood.Among these,asthenia of heart qi and yang is the the key of pathogenesis,deficiency of spleen and kidney is central segment,phlegm turbidity and blood-stasis are present during the through course.5.3 We should strengthen body resistance to dispel pathogenic factors, be weighed against the lack of qi blood yin and yang,adjusting the partial failure of internal organs,especially paying attention to replenishing heart Qi and Wen Tong Xin Yang.At the same time,we should regulate Qi,activate the blood,Wen Tong and dissolve phlegm flexibly according to the actual situation,especially activating blood circulation and dredging the collaterals.In a word,Replenishing Qi,Warming Yang,Resolving Stagnation Therapy was emphasizing in particular.5.4 This clinical observation confirms that Replenishing Qi,Warming Yang, Resolving Stagnation Therapy can significantly alleviate the patients’ clinical symptoms such as chest tightness,chest pain,etc.It can improve quality of life,reduce FPG and 2hPG,improve the state of myocardial ischemia, correct the disorders of lipid metabolism and reduce serum cystatin C.5.5 Its mechanism may be correlated with the regulation of glucose metabolism,correct the disorders of lipid metabolism,improve the state of myocardial ischemia and protect cardiac and renal function.5.6 The results show that the treatment group can reduce the level of serum Cys C.Dynamic detection of serum Cys C can be an index,the level of serum Cys C can provide reference for clinical medication because it can reflect the severity of CHD to a certain extent,it is an important predictor for secondary cardiovascular events and the risk of death among patients with known CHD.The relationship between Serum Cys C and DM with CHD also need more in-depth research,its mechanism remains to be further explored.Clinically,Cys C should be combined with other indicators of a comprehensive analysis,in order to make an objective assessment of development and prognosis of DM with CHD.5.7 During the course of the study,we have not found any adverse reactions.We think that this traditional Chinese medicine is safe and sure.This preliminary observation shows that traditional Chinese medicine has the following advantages,such as alleviate clinical symptoms,improve quality of life and amelioration clinic laboratory tests.Replenishing Qi,Warming Yang,Resolving Stagnation Therapy used in treating DM with CHD has the exact clinical efficacy,which is safety and hit the pathogenesis.So it is worthy of spreading.更多还原