【作者】 区绮云；

【导师】 陈群；

【作者基本信息】 广州中医药大学 ， 中医学， 2008， 博士

【摘要】 舌下络脉诊法主要观察舌腹面的变化,用以判断人身气血盈亏瘀畅,为辨证辨病提供更为丰富的诊断信息。本课题以妇女子宫内膜异位症为研究对象,采用前瞻性手段,通过文献研究、临床观察、实验研究、舌象图像分析、临床流行病学/DME诊断试验评价等方法,探讨子宫内膜异位症与舌下络脉异常的关系,以求实现运用舌下络脉诊法结合症状体征较早较准确地诊断子宫内膜异位症,为确定舌下络脉诊法对疾病血瘀证的诊断准确率的进一步深入研究奠定基础。论文分为五个部分:第一部分文献研究系统地整理和研究了古今中外与舌下络脉相关的文献。舌下络脉的记载肇始于《内经》,作为一种诊法兴于晋隋唐宋,衰落于明以后,新中国成立后得以复兴。古代医家已认识到多个脏腑通过经脉与舌下络脉相连,舌下络脉变化对某些疾病具有诊断意义,并把舌下络脉作为治疗部位广泛应用于临床。现代医家分别从基础及临床应用等方面对舌下络脉进行研究。临床对舌下络脉异常与各种内科病关系的研究较多,有关子宫内膜异位症与舌下络脉关系的研究相对较少。部分研究探讨了子宫内膜异位症舌下络脉异常以及用活血化瘀治疗后的舌下络脉的变化情况,多数从病因病机及形成机理方面阐述内异症与血瘀证的关系。这些研究成果为内异症血瘀证型的诊疗起到积极的作用。但尚未见到有将文献、临床、实验与诊断准确性评价等融合起来,系统研究内异症与舌脉异常关系的报道。第二部分临床研究1子宫内膜异位症舌下络脉的临床研究研究目的:探讨子宫内膜异位症血瘀证舌象的临床特征。研究对象:子宫内膜异位症患者85例,子宫肌瘤患者85例,健康人30例。研究方法:采用前瞻性研究方法,将临床观察结果与计算机图像自动识别分析相结合。研究结果与讨论:本研究结果显示,子宫内膜异位症及子宫肌瘤组患者的舌背面与一般瘀血舌象的病理变化相似,单凭观察舌质难以判别二者:舌苔的变化与血瘀证的兼证关系密切,对分辨子宫内膜异位症不同证型有重要价值。子宫内膜异位症与子宫肌瘤患者舌质RGB颜色空间主要表现为R值的降低和B值的升高,而子宫内膜异位症患者舌质的R值比子宫肌瘤患者的更低,B值更高。子宫内膜异位症患者存在严重的舌下络脉异常,总积分平均超过10分的占研究对象的90.59%,远高于子宫肌瘤患者68.24%的异常率。我们认为,综合观察舌脉的色泽、宽径、长度、形态、充盈度及外带是诊断子宫内膜异位症的一个重要指标。2子宫内膜异位症的腹腔镜探查及治疗研究目的:探讨子宫内膜异位症腹腔镜下诊断及治疗情况。研究对象:子宫内膜异位症患者85例。研究方法:全自动可视系统下行腹腔镜手术。研究结果与讨论:85例患者均在腹腔镜下完成手术,有81例确诊为子宫内膜异位症。我们认为腹腔镜手术创伤少,对微小病灶有很大优越性。操作灵活,处理卵巢囊肿及腹膜内异症病灶有效、快捷,伤口愈合快。但它是有创伤性手段,不能作为常规检查;设备及手术昂贵,很多医疗机构及患者无法承担;不能根治,患者术后复发的可能性较高,故未能普及。应用无创的舌诊法,尤其是舌下络脉诊法对于筛查及指导子宫内膜异位症临床诊疗有重要的实践价值。第三部分临床实验研究研究目的:探讨子宫内膜异位症及子宫肌瘤患者舌下络脉变异的病理机制。研究对象:子宫内膜异位症患者85例,子宫肌瘤患者85例,健康人30例。研究方法:空腹静脉采血检测以下指标:（1）纤维蛋白原（FIB）的测定:Clauss法;（2）雌二醇（E₂）、催乳素（PRL）的测定:微粒子化学发光酶免疫分析法;（3）癌抗原125（CA125）、糖类抗原19—9（CA19—9）的测定:微粒子化学发光酶免疫分析法;（4）抗子宫内膜抗体（EmAb）的测定:ELISA法。研究结果与讨论:1子宫内膜异位症组FIB、E₂、PRL高于正常值。FIB显著高于对照组及子宫肌瘤组,说明内异症患者血液呈高凝状态,FIB升高是内异症血瘀形成的重要因素,反映在舌象上则为瘀血舌及舌下络脉异常改变。子宫内膜异位症与子宫肌瘤患者E₂水平均高于正常范围,说明二者均属于雌激素依赖性疾病。二者雌激素升高无统计学差别。子宫内膜异位症组PRL值显著高于对照组及子宫肌瘤组。认为E₂对PRL的影响及二者的共同作用是促进子宫内膜异位症发生发展的重要因素。同时,PRL所引发或促进血液流变学的改变,与中医血瘀表现相似,印证了中医认为内异症是血瘀证,其治疗应以活血化瘀为大法。子宫肌瘤患者PRL在正常范围内较对照组升高,认为可能是受高E₂的影响。所以,高E₂、高PRL为子宫内膜异位症的重要特征。2血清CA125、CA19-9及EmAb在本组子宫内膜异位症患者中的表达水平总体不太高,分别只有63.5%、50.6%和51.8%。Ⅰ～Ⅱ期轻度患者中CA125、CA19—9的平均值仍属正常,阳性率更低,说明CA125、CA19-9无法对轻度子宫内膜异位症患者作出准确判断。随子宫内膜异位症病情的加重,CA125、CA19-9、EmAb的表达水平越高,故认为三者在预测子宫内膜异位症严重程度上的价值大于诊断价值。临床结合其中两项或三项同时检测,可提高对子宫内膜异位症诊断的准确性。第四部分应用舌下络脉诊查子宫内膜异位症准确程度的计算研究目的:探讨应用舌下络脉诊查子宫内膜异位症的准确程度。研究对象:子宫内膜异位症患者85例。研究方法:遵循DME方法中的诊断试验方法,以腹腔镜为金标准,将舌下络脉与临床实验结果比较,计算舌下络脉诊查子宫内膜异位症的敏感度、特异度、漏诊率、误诊率、准确度、似然比等指标。研究结果与讨论:计算以上指标,得出舌下络脉诊法对内异症的诊断敏感度、特异度、阳性似然比均比较高,漏诊率、误诊率及阴性似然比较低,提示以舌下络脉作为一项诊断子宫内膜异位症的指标是有意义的。与腹腔镜相比,舌下络脉诊法的准确度为92.94%,反映了舌下络脉诊法与腹腔镜诊断相符合的程度非常高。本研究中舌下络脉诊法诊断子宫内膜异位症的准确性要优于诊断子宫肌瘤的准确性。第五部分结语本研究的创新性:（1）首次以子宫内膜异位症患者舌背面及舌下络脉为研究对象,从整体、分子等不同水平探讨了子宫内膜异位症舌象尤其是舌下络脉的临床特征和形成因素,为子宫内膜异位症患者血瘀证的诊断、治疗、预后分析提供了客观依据;为特定人群作子宫内膜异位症筛选后再行腹腔镜,可减少创伤及负担。（2）运用临床流行病学/DME诊断试验方法进行设计及研究,最大限度地降低偏倚和机遇带来的随机误差影响,初步证明中医舌诊法,尤其是舌下络脉诊法应用于现代疾病诊疗的可行性及准确性。（3）拓宽了瘀血舌象及血瘀证的研究思路,同时也为建立瘀血舌象诊断标准及标准的顺利实施探索了一种重要的研究方法。更多还原

【Abstract】 The visual inspection of a patient’ s sublingual veins mainly gauges the waxing and waning of qi and blood,offers more information for differentiation of syndromes and diseases.This study took women’ s endometriosis as the research object,discussed the relationship between endometriosis and pathological variations of sublingual veins by the means of prospective study and by the methods of literature research,clinical research,experimental study,diagnostic tests and evaluation of clinical epidemiology and so on, in order to diagnose endometriosis early and exactly by observing and analyzing sublingual veins combining symptoms and signs,laid the foundation for further research of blood stasis diseases’ diagnostic accuracy.The thesis is divided into five parts.Part 1 Literature ResearchReorganized and studied systematically the literatures which were correlated with sublingual veins of all times and in all countries.The original record of sublingual veins was seen in the book of The Yellow Emperor’s Medicine Classic（Huang Di Nei Jing）.As a diagnostic method,the visual inspection of a patient’ s sublingual veins rose in dynasties Jin Sui Tang Song,paused after dynasty Ming,revitalized in new China.Ancient doctors had realized lots of viscera link sublingual veins by meridians and collaterals, the variations of sublingual veins connect with some diseases,and sublingual veins as a treatment site be wildly used in clinical.Modern doctors have researched sublingual veins in base and clinical.There have been major clinical researches concerned with relationships between sublingual veins and kinds of internal diseases,and relatively minor about the relationships between sublingual veins and endometriosis.A part of these researches discussed pathological sublingual veins of endometriosis and variations after treating with activating blood to resolve stasis.Most of them clarified the connection of endometriosis and blood stasis syndromes in etiology and pathogenesis.These results played positive roles on diagnosing and treating endometriosis.But there have no reports of systematic researches on relationship between endometriosis and pathological sublingual veins by the method of literature research,clinical research,experimental study and accuracy evaluation of diagnosis and so on.Part 2 Clinical Research1 Clinical Research on Sublingual Veins of EndometriosisObjective:to explore the clinical characteristics of endometriosis patients’ tongue in blood stasis syndrome.Object:85 cases with endometriosis,85 cases with hysteromyoma,30 healthy cases as control.Method:The prospective study was made.The clinical observation and the automatic recognition and analysis of image by computer were combined.Results and Conclusions:Clinical observation showed that pathological variations on the back of tongue of endometriosis patients and hysteromyoma patients are similarly as general tongue of blood stasis.Just observing the tongue body is difficult to distinguish these two diseases.The variety of tongue coating relates closely to deputy syndrome of blood stasis and plays an important role in judging different syndrome of endometriosis.R,G,B values of the tongue body of endometriosis patients and hysteromyoma patients mainly performed as R values descending and B values ascending.Descending in R values and ascending in G values of the tongue body of endometriosis patients were much than hysteromyoma patients.There were serious pathological variations of sublingual veins in endometriosis patients.Total scores of pathological sublingual veins of endometriosis participants,there were 90.59%beyond 10 scores on average.The pathological rate was much than 68.24% of hysteromyoma participants.It was thought that comprehensively observing color,wild diameter,length,shape,filling and outer of sublingual veins is an important indicator in diagnosing endometriosis.2 Using Laparoscopy to Explore and Treat EndometriosisObjective:to explore using laparoscopy to diagnose and treat endometriosisObject:85 cases with endometriosis.Method:Operating in automatic and visualized system by laparoscopy. Results and Conclusions:85 cases finished surgery by laparoscopy,and 81 cases were confirmed as endometriosis.We thought that there were lots of benefits of surgery by laparoscopy,such as little traumas,much superiority to minute lesions,flexible operation,more effective and efficient in treating ovary cysts and peritoneal endometriosis lesions and make wound healing easily.But it is a traumatic means couldn’t be a wellness check.It is expensive that many hospitals and patients couldn’t afford.Laparoscopy surgery can not completely cure endometriosis that can not be universal.Applying no injuries about tongue diagnosis especially sublingual veins in TCM has significant practical values in screening and guiding clinical diagnosis of endometriosis.Part 3 Clinical Experimental StudyObjective:to explore the pathologic mechanism of sublingual veins changes of endometriosis patients and hysteromyoma patients.Object:85 cases with endometriosis,85 cases with hysteromyoma,30 healthy cases as control.Method:hemospasia venous blood on fasting to examine the following indexes:（1）Fibrinogen（FIB）:Clauss;（2）Estrodial（E₂）,Prolactin（PRL）:Micro particle of immunoassay chemiluminescence;（3）Carbohydrate Antigen 125（CA125）,Carbohydrate Antigen 19-9（CA19-9）: Micro particle of immunoassay chemiluminescence;（4）Endometrial Antibody（EmAb）:ELISA.Results and Conclusions:1 The FIB,E₂ and PRL of the endometriosis group are higher than the normal range,and FIB notable higher than the control group and the hysteromyoma group. These showed endometriosis patients’ blood being hypercoagulability. Increasing of FIB is an important factor in the formation of endometriosis blood stasis,which reflecting on tongue is the tongue of blood stasis and pathologic variations of sublingual veins.E₂ level of endometriosis group and hysteromyoma group were higher than the normal range,proofing that either of them are belong to estrogen-dependence-disease.There was no statistics difference of their estrogen increasing.PRL level of endometriosis group was much higher than the control group and the hysteromyoma group.It is thought that E₂ infecting PRL and combined working of them made a significant role in promoting the occurrence and development of endometriosis.Otherwise,the changes making or promoting by PRL are likely as the performance of blood stasis of TCM.It confirmed endometriosis being blood stasis syndromes as TCM sees, and its main treatment must be activating blood to resolve stasis.PRL level of the hysteromyoma group was in normal range but higher than the control group, being thought infected by high E₂ level.Therefore,high E₂ and PRL level was an important feature of endometriosis.2 CA125,CA19-9 and EmAb levels in serum of endometriosis participants in this study were not too high,were only 63.5%,50.6%and 51.8%.Average level of CA125 and CA19-9 of mild patients in stageⅠ～Ⅱwas still in normal range and their positive rate was low.It could say that the expression of CA125 and CA19-9 can not judge endometriosis accurately.With illness increasing,CA125,CA19-9 and EmAb expressed higher and higher.It is thought that three of them had much value in forecasting the extent of illness than diagnosing endometriosis.Combining detection two of them or three of them in clinical can improve accuracy of endometriosis diagnosis.Part 4 Accuracy Estimate of Applying Sublingual Veins to Diagnose EndometriosisObjective:to explore the degree of accuracy of applying sublingual veins to diagnose endometriosis.Object:85 cases with endometriosis.Method:following the diagnostic test method of DME,making laparoscopy results as gold standard,comparing clinical results with variations of sublingual veins,estimating diagnostic indexes of sublingual veins such as sensitivity,specificity,misdiagnosis rate,missed diagnosis rate,accuracy, likelihood ratio and so on.Results and Conclusions:Calculated the indexes above,the results of diagnostic sensitivity, specificity,and positive likelihood ratio were relatively high and misdiagnosis rate,missed diagnosis rate,negative likelihood ratio were relatively low by applying sublingual veins to diagnose endometriosis.It conformed that,as an endometriosis diagnosis index,applying sublingual veins is significant.Compared with laparoscopy results,the accuracy of sublingual veins diagnosis was 92.94%,reflected that sublingual veins diagnosis is high match with laparoscopy diagnosis.In this stud,the accuracy of sublingual veins diagnosis in endometriosis diagnosis was better than in hysteromyoma diagnosis.Part 5 SummaryThe innovation in this study is:（1）This study took tongue back and sublingual veins of endometriosis patients as the research object for the first time,explored the clinical characteristic and the mechanism of formation of endometriosis patients’ tongue from different levels of entirety,molecule and so on,and provided the objective basis for the diagnosis,treatment, prognosis analysis of endometriosis.It could be a screening for specific group of people,and could decline trauma and economical burden.（2）Appling clinical epidemiological diagnosis tests method to design and research could maximum decline infection of bias and opportunities.It was initial proofed tongue diagnosis,especially sublingual veins diagnosis of TCM can feasible and accurately be used in diagnosing modern diseases.（3）The study opens up the thought of research on tongue of blood stasis and blood stasis syndrome,and also explores an important method of establishing diagnostic standard of tongue of blood stasis and carrying out the standard successfully.更多还原