【作者】 秦文敏；

【导师】 罗颂平；

【作者基本信息】 广州中医药大学 ， 中医妇科学， 2009， 博士

【摘要】 反复自然流产(滑胎)是全世界共同关注的疑难病症,也是妇科常见病之一,其发病率占到生育年龄妇女的0.4%-0.8%。不仅损害妇女的身心健康,甚至还可能引发一系列家庭问题,而给社会带来不稳定的因素,因此研究反复自然流产的防治方法具有积极的临床意义和社会意义。目前除已知的解剖、免疫等因素外,尚有60%的反复自然流产原因不明,而且目前国内外尚无治疗反复自然流产的理想方法和药物,故防治反复自然流产如今已成为医学界的共同关注的热点。而中医药对防治滑胎等方面有独特的优势,在治疗上取得了良好的临床效果。中医药是一个伟大的宝库,古今中医文献中就包含有诊治本病的宝贵经验,很值得我们去挖掘。本文从古今文献的整理和方药应用分析等理论研究入手,总结反复自然流产(滑胎)古今文献研究概况及古今方药证治规律等,以期对科研及临床用药提供有益的参考。一、反复自然流产的文献研究本文运用中医文献学“辨章学术,考镜源流”的研究方法,运用检索和分析的手段,对各类资料进行分类研究。历代文献的研究提示:滑胎作为妇科一个疾病名称始于清代,作为治疗方法要早于作为疾病名称一千余年。滑胎的原因侧重于母体冲任损伤,气血虚衰、内伤七情、房劳多产、饮食不节等均可造成滑胎。病机的论述多侧重于脾肾两虚,另外、肝郁、血瘀、血热等也是不可忽视的因素。在治则治法上多侧重于补肾健脾的药物治疗等,在妊娠期间应予以避忌或慎用的妊娠禁忌中药,历代医家也认为并不绝对避讳妊娠期应用禁忌药,明示妊娠期胎动不安,若能做到辨证求因,用药恰当,则妊娠禁忌药亦可收到安胎良效。在预防与康复上提出,应注意精神调养、饮食起居保养、节制性欲、慎用药物、男女双方适龄而婚等思想。近20年的文献研究提示:在病因病机方面不仅注重母体因素,如生殖器官异常、感染因素、内分泌功能异常等,胎儿因素如遗传因素、胎盘异常等导致滑胎也论述至深,值得借助科技手段进行深入探讨与研究;“预防为主,防治结合”的治则也是值得当代医生注意的问题;在治法上虽然专病专方治疗值得研究,但应提倡辨病与辨证相结合。另外,对中药保胎的预后进行了临床及实验研究观察,得出中医药保胎安全、可靠、疗效确切,对小儿智力及体格发育无不良影响的结果。近20年的文献研究还分为理论研究、临床研究和实验研究三部分进行归纳整理。理论研究:病因学方面对内分泌、免疫因素的研发究有了长足的进展。临床研究:对辨病和辨证结合有了初步的理论探讨,并进行了中药保胎预后疗效的追访观察。实验研究:现代中医学者已掌握了先进的科学技术,使中医对反复自然流产的研究提高到了分子水平。二、方药证治规律研究通过对古今方药进行统计学方法的分析,总结治疗反复自然流产的主要证治方药的运用情况和证治特点,以探讨反复自然流产的辨证论治及遣药组方的规律,为临床用药提供参考,以对本病相关文献研究和理论完善有所裨益。(一)古代方药证治规律的研究1研究方法古代方药的选择以《中医方剂大辞典》为主要检索目标,筛选了上至东汉,下至清末民国期间的有关治疗滑胎的方药文献资料。建立数据库,运用统计学方法,进行用药频数、聚类等分析,总结其方药证治规律。2研究结果(1)宋代以前方药统计分析结果中,用药以当归,川芎,白术,人参,甘草等药物使用频数较高;以补益药(34.7%)、温里药(11.1%)、疏肝解郁药(11.1%)、收涩药(9.7%)所占比例较大,累积频率达到66.7%。用药偏于温平(63.9%),以甘味(40.7%)为主;药物归经主入肝(16.8%)、肾(15.9%)、脾(15.0%)为主;聚类分析药物组合中,以治疗气血虚衰,气虚不固以及肾虚不固之滑胎为主。第一类药物:当归、川芎、白术、甘草、人参、生姜。当归。第二类药物:白芍、熟地黄、吴茱萸、黄芩、乌梅、五味子。(2)宋金元时期方药统计分析结果中,用药以熟地黄、当归、阿胶、白术、人参等药物使用频数较高;以补益药(24.O%)、疏肝解郁药(14.6%)、温里药(10.9%)、清热药(9.4%)、活血化瘀药(7.8%)所占比例较大,累积频率达66.7%,用药偏于温平,以温(52.1%)为主,药味以辛(33.9%)为主;药物归经主入肝(19.9%),其次归脾经(15.9%)和肾经(15.9%);聚类分析药物组合中,以治疗气血虚衰、气滞血瘀之滑胎较为多见。第一类药物:熟地黄、当归、五味子、黄芪、桂皮、白芍、人参、甘草。第二类药物:续断、山药、杜仲、桑寄生。第三类药物:青皮、玄胡、赤芍、阿胶、山萸肉、蒲黄。第四类药物:黄芩、生地黄、麦冬、石斛、厚朴、生姜、艾叶、干姜。(3)明清时期方药统计分析结果中,用药以当归、白术、白芍、川芎、熟地黄等药物使用频数较高;以补益药(49.6%)、清热药(10.3%)、活血化瘀药(9.5%)、理气药(7.7%)所占比例较大,累积频率达77.1%,用药偏于温(49.2%),以甘味(48.2%)为主;药物归经主入肝(20.4%),其次归脾经(18.3%)和肾经(16.7%);聚类分析药物组合中,以治疗气血两虚,冲任不固之滑胎为主。第一类药物:当归、白术、茯苓、山药、黄芪、陈皮、白芍、熟地。第二类药物:黄芩、杜仲、续断、人参、甘草、生地黄、桑寄生、苏梗。第三类药物:川芎、阿胶、丹参、山茱萸、干姜、艾叶。第四类药物:菟丝子、五味子、香附、生姜、大枣。(4)近代方药统计分析结果中,用药以当归、白术、甘草、白芍、黄芩等药物使用频数较高;以补益药(43.7%)、清热药(13.5%)、理气药(12.6%)、疏肝解郁药(10.2%)所占比例较大,累积频率高达80.0%;用药偏于温平,以甘苦之味为主;药物归经主入肝经(26.2%)为主,其次归肾经(22.6%)和脾经(16.1%);聚类分析药物组合中,以治疗脾肾亏虚之滑胎为主。第一类药物:当归、白术、茯苓、人参、川芎、阿胶、甘草。第二类药物:白芍、黄芩、续断、杜仲、砂仁、生地黄。第三类药物:艾叶、熟地黄、黄芪、菟丝子、桑寄生、益母草。3结论历代滑胎证治方药的药物频数提示以补益药为主,清热药、温里药、疏肝解郁药的使用比例和频率也较高,药性以温平为主,药味以甘为主,主归肝经;方药聚类组合体中,常常涉及补益、清热、固涩及温里等四大类中药,具有补肾健脾、益气养血、清热养阴、收敛固涩等功效,对于治疗滑胎等病证具有提示作用,反映了本病本虚为主、虚实错杂的病因病机及证治特点。(二)现代方药证治规律研究1研究方法现代方剂的选择以维普数据库为主要检索途径,结合图书手工检索的方式,对近30年来的重要期刊杂志以及重要书籍所报道的有关中医药治疗反复自然流产的临床文献进行筛选,规范数据,建立数据库,运用统计学方法,进行用药频数、聚类等分析,总结其方药证治规律。2研究结果在选方用药方面,以补虚药为主,尤其是补气与补阳药,清热药、止血药、收涩药兼顾,所用药物的四气以温为主。从整体而言,温热之性大于寒凉之性。药物归经以肝、肾和脾为主。方药聚类组合体中,以补益为主,兼顾清热、固涩等,具有补肾健脾、清热养阴、生津止渴、收敛固涩等功效。第一类药物:菟丝子、桑寄生、白术、续断、甘草、阿胶。第二类药物:当归、白芍、熟地黄、苏梗、茯苓、五味子。第三类药物:黄芪、党参、杜仲、生姜、大枣、砂仁、巴戟天。第四类药物:人参、川芎。第五类药物:黄芩、山萸肉、陈皮、丹参、赤芍、山药、紫河车。三、结论对于古代和现代治疗反复自然流产(滑胎)方药分析,提示以补益药、温里药、清热药、收涩药等的使用比例和频率较高,药性以温平为主,药味以甘为主,主归肝肾脾经;方药聚类组合体中,主要有补益、清热、活血、温里、行气等几类药,具有补肝肾脾、益气养阴、活血化瘀、温里收涩等功效,反映了滑胎本虚为本、虚实错杂的病因病机特点和补益为主、兼祛实邪的证治规律。而古今证治方药的发展变化,以补益药使用频率的大大增加最为显著。根据文献研究和统计分析的结果,结合中医理论,在导师的指导下,对反复自然流产的病因病机、治则治法等进行了系统整理,分析梳理了证治与用药规律,并归纳了安胎常用中药与方剂。更多还原

【Abstract】 Recurrent Spontaneous Abortion(RSA)is clinical common and one of the stubborn diseases that the whole world pay attention to.Its’attack rate has reached to 0.4%--0.8%in reproductive aging women.It not only harms their physical and mental health,even causes lots of family problems,which are dangerous to the society.So it has the positive clinical and social meaning of the research on RSA.At present,except the anatomy and immunity aspects, 60%reasons of RSA are unknown.There is no ideal drugs and method in treating RSA at home and abroad.So now it has become common concern hot spot of the medical profession about how to prevent and treat RSA effectively.However Traditional Chinese Medicine(TCM)not only has its unique advantages on preventing and treating RSA,but also has made a good clinical effect.TCM is a great treasure house,ancient and modern literature of TCM about RSA included the valuable diagnosis and treatment experience which is worth to mine.The paper from ancient and modern literature collation and analysis of prescriptions with theoretical study starts,concluded ancient and modern literature research overview,syndromes and treatment regular of prescription of RSA,with a view to provide a clinical useful reference.1 Relevant Literature researched and differentiated of Traditional Chinese Medicine of Recurrent Spontaneous AbortionThe author used TCM documental study of“discriminating thoughts among different academic schools and probing academic origin”combining with textual research and modern analytic method,and gave classified study of all kinds information.The document study in different dynasties showed“Huatai”as the denotation of RSA began from the Qing Dynasty while as the treating means started more than 1000 yeas ago.The reason of RSA lays particular emphasis on the damage of the Cbongren of the mother,the asthenia of Qi and blood,grieved feelingand lots of birth also causeRSA.Thepathogenesis pays more attention to the astheniaof the kidney and spleen.In treating methods, replenishing drugs much used in treating RSA.Taboo medicine also can be used in case of correct diagnosis.In precaution and rehabilitation,spirit nursing, rest in daily life,sexual desire restraining and marriage in appropriated age should also pay attention to.The document study of 20 recent years showed in etiology there were much deep study in not only parent factors such as the abnormality of the reproductive organ,infection factor endocrine factor but also fetal factors, such as the abnormality of the fertilized ovum and the placenta which is worth further studying by scientific technique.And the pathogenesis of deficiency of kidney and spleen is important,blood-stasis,blood-heating should also consider.The principle of paying much attention to precaution and combining precaution and treating is worth thinking highly of for doctors.Although special recipe for special disease need further study,we should advocate differential diagnosis.The prognosis of tocolysis by traditional Chinese Medicine shows the therapeutic effect is safe.Documental study of 20 recent years canbe classified in three sections:theoretical study,clinical study and laboratory study.In etiology of theoretical study,there were significant development in the study of endocrine secretion and immunology.A breakthrough in clinical study should belong to traditional medicine treatment combined with different diagnosis.The most encouraging thing in laboratory study is modern TCM doctors get hand of up-to-date scientific techniques,and enhance studying level of traditional Chinese gynecological theory to molecular level.2 Study on the laws of syndrome differentiation and treatment of prescriptionsThrough analysis of statistical methods for the ancient and modern prescriptions,sum up the using condition and characteristics of these prescriptions treating RSA,to explore the regularity of syndrome differentiation and treatment and removal of the drug group about RSA,for clinical drug reference,and be benefit to the literature research and theoretical improvement on this disease.ⅠThe laws of syndrome differentiation and treatment of ancient prescriptions (Ⅰ)Method Ancient prescriptions’choice as A dictionary of Chinese Medicine Prescription for the main research goal,screened up to the Eastern Han Dynasty, down to the end of the Qing Dynasty and republic prescription literature data about the treatment of RSA.Standardize data,establish prescription database, and make analysis of frequency of use、cluster through the use of statistical methods to sum up its syndrome and treatment regularity of prescription.(Ⅱ)ResultsIn the statistical analysis of prescription of results before the Song dynasty,medication to Chinese Angelica,Szechwan Lovage Rhizome,Largehead Atractylodes Rhizome,Ginseng,Radix Glycyrrhizae;there is the larger proportion to replenishing drugs(34.7%),drugs for warming interior(11.1%), drugs for relieving exterior syndrome(11.1%)and drugs for arresting discharge(9.7%),cumulative frequency up to 66.7%;medication Partial to warm and bland;mainly to sweet taste;the drugs mainly into the liver meridian (16.8%),the kidney meridian(15.9%)、the spleen meridian(15.0%);in drug combinations by cluster analysis,to mainly treat the RSA caused by the asthenia of Qi and blood and kidney debilitation.In the statistical analysis of prescription of results during the Songjinyuan Dynasty,medication to Prepared Rehmannia Root,Chinese Angelica, donkey-hide glue,Largehead Atractylodes Rhizome,Ginseng;there is the larger proportion to replenishing drugs(24.0%),drugs for warming interior(10.9%), heat-clearing drugs(9.4%),stasis-eliminating drugs(7.8%),cumulative frequency up to 66.7%.medication Partial to warm and bland;mainly to sweet taste;the drugs mainly into the liver meridian(19.9%)、the kidney meridian(15.9%)、the spleenmeridian(15.9%);in drug combinations by cluster analysis,to mainly treat the RSA of kidney deficiency and the asthenia of Qi and blood.In the statistical analysis of prescription of results during the Ming and Qing dynasty,medication to Chinese Angelica,Largehead Atractylodes Rhizome,White peony Alba,Szechwan Lovage Rhizome Prepared Rehmannia Root; there is the larger proportion to replenishing drugs(49.6%),heat-clearing drugs(10.3%),stasis-eliminating drugs(9.5%),Qi regulating drugs(7.7%), cumulative frequency up to 77.1%.medication Partial to warm,mainly to sweet taste;the drugs mainly into the liver meridian(20.4%)、the spleen meridian (18.3%)、the kidney meridian(16.7%);in drug combinations by cluster analysis, to mainly treat the RSA of deficiency of Qi and blood.In the statistical analysis of prescription of results during the modern times,medication to Chinese Angelica,Largehead Atractylodes Rhizome,Radix Glycyrrhizae,White peony Alba,Baical Skullcap Root;there is the larger proportion to replenishing drugs(43.7%),heat-clearing drugs(13.5%),Qi regulating drugs(12.6%),drugs for relieving exterior syndrome(10.2%),cumulative frequency up to 80.0%.medication Partial to warm and bland;mainly to sweet and bitter taste;the drugs mainly into the livermeridian(26.2%)、the kidney meridian(22.6%)、the spleen meridian(16.1%);in drug combinations by cluster analysis,to mainly treat the RSA of deficiency of kidney and spleen.(Ⅲ)ConclusionAnalysis from syndrome differentiation and treatment prescriptions’ distribution of RSA indicates that there is higher using proportion and frequency for heat-clearing drugs,drugs for warming interior,Qi regulating drugs,mainly to replenishing drugs,medication Partial to warm and bland; mainly to sweet taste,the drugs mainly into the liver meridian;in drug combinations by cluster analysis,often involves four drug category such as replenishing drugs,heat-clearing drugs,drugs for warming interior,drugs for arresting discharge,with invigorating and consolidating the kidney and spleen,heat-clearing and nourishing yin,it reflects the feature of asthenia in origin and sthenia in superficiality and deficiency syndrome mingling with excess syndrome about cause and pathogenesis of disease and syndrome differentiation and treatment.Overall,about the concept of RSA、prescription of syndrome differentiation and treatment and the development process.ⅡThe laws of syndrome differentiation and treatment of 30 recent years prescriptions(Ⅰ)Method20 recent years prescriptions’choice as VIP database for the main search way,with manual retrieval of books,screened important magazines,journals with the relevant experts and important books in recent 30 years reported in clinical literature of Chinese Medicine treatment of RSA.Standardize data, establish prescription database,and make analysis of frequency of use、cluster through the use of statistical methods to sum up its syndrome and treatment regularity of prescription. (Ⅱ)ResultsFrom the statistical analysis of the prescription of results of contemporary era,it is found that there is higher using proportion and frequency for replenishing drugs,heating-clearing drugs,exterior syndrome relieving drugs medication partial to warm and bland,mainly to sweet taste, the drugs mainly into the liver,spleen,kidney meridians.In drug combination by cluster analysis,it often involves four drug categories,such as replenishing drugs,heating-clearing drugs,exterior syndrome relieving drugs and drugs for arresting discharge.,with invigorating spleen and consolidating kidney,heat-cleaning and nourishing yin,promoting the production of body fluid to quench thirst.3 ConclusionAnalysis from prescriptions about RSA indicates that there is higher using proportion and frequency for replenishing drugs,heat-clearing drugs, drugs for warming interior,Qi regulating drugs,medication partial to warm and bland;mainly to sweet taste,the drugs mainly into the liver、the kidney、the spleen meridian;in drug combinations by cluster analysis,mainly involves drug category such as replenishing drugs,heat-clearing drugs,activating blood circulation drugs,with tonifing the liver and kidney and spleen, benefiting vital energy and nourishing yin,activating blood circulation to dissipate blood stasis,reflecting the feature of asthenia in origin and sthenia in superficiality,deficiency syndrome mingling with excess syndrome about cause and pathogenesis of the RSA,the laws of syndrome differentiation and treatment of replenishing healthy energy mainly and eliminating sthenia pathogenic factors.However,about the development and changes of ancient and modern prescriptions of the laws of syndrome differentiation and treatment,it is most significant that the using frequency of drugs replenishing drugs greatly increased.According to ancient and modern exposition and knowledge learning from Tutor Luo,the author discussed the female genital theory and the etiology and pathogenesis of RSA.To make the diagnosis of RSA comprehensive,systematic, clear;to make the treatment system that combines the disease and the syndrome in TCM more reasonable.更多还原