【作者】 胡向丹；

【导师】 黄健玲；

【作者基本信息】 广州中医药大学 ， 中医妇科学， 2009， 博士

【摘要】 研究背景PCOS是育龄期妇女常见内分泌性综合征,发病率高达5%-10%,其中肥胖型比率高达50%,胰岛素抵抗发生率为50-70%,占发病患者的绝大部分,过量的胰岛素作用于卵巢内相应受体,引起卵泡发育和成熟障碍,无优势卵泡形成,从而导致不排卵及不孕,故患者出现月经稀发、闭经、痤疮、多毛、肥胖、不孕等症状。目前认为胰岛素抵抗和高胰岛素血症在多囊卵巢综合征发病中起到关键的作用,而胰岛素抵抗为临床多种疾病的高危因素,可导致糖尿病、心血管疾病和子宫内膜癌的发病率升高,远期危害性高,积极探索寻找PCOS合并IR有效的、副作用少并且对远期并发症起到良好预防作用的治疗方法具有重要意义。我院省名老中医李丽芸教授根据前人论述,结合自己多年的临证经验,提出多囊卵巢综合征的病机以肾虚为本,血瘀及痰阻为标,属虚实夹杂之证,故以补肾导痰活血为法治疗多囊卵巢综合征,并创立了经验方且已制成院内制剂灵术颗粒和参芪胶囊。前期研究表明,经验方灵术颗粒和参芪胶囊对治疗PCOS确有疗效。穴位埋线是近年兴起的针灸绿色疗法,以其简便廉验为特色,在肥胖病的治疗研究上取得一定成效。检索文献,目前对中药联合穴位埋线治疗多囊卵巢综合征临床疗效、作用机理以及对PCOS远期并发症方面相关危险因素IR、肥胖、血脂等的干预作用报道非常少,并且疗效评定标准各不相同,尚缺乏系统性和规范性的研究。因此针对目前中医对PCOS研究现状,以及西药应用方面缺陷,我们设想创立一种中药联合穴位埋线治疗PCOS的新方法,借助穴位埋线对肥胖方面良好的治疗作用及李丽芸教授治疗PCOS经验方灵术颗粒,评估联合两种治疗方式在干预及治疗PCOS及其远期并发症的部分高危因素方面能否发挥重要作用。研究目的本研究旨在通过比较李丽芸教授经验方灵术颗粒与目前西医治疗PCOS合并IR的最常用药物二甲双胍以及灵术颗粒联合穴位埋线治疗多囊卵巢综合征的临床疗效差异,通过观察月经、排卵、体质量、生殖内分泌、胰岛素抵抗、血脂等的改善情况,对灵术颗粒以及灵术颗粒联合穴位埋线治疗多囊卵巢综合征的临床疗效作出客观评价、探讨其可能的作用机制。为临床提供PCOS有效的、副作用少并且对远期并发症起到良好预防作用的治疗方法奠定理论基础。研究方法本研究采用前瞻性临床对照试验研究,选择2008年2月至2009年2月广东省中医院妇科门诊就诊的符合诊断和纳入标准的PCOS合并IR的患者77例,设立中药治疗组、西药组、针药结合组。其中中药组28例,采用经验方灵术颗粒(广东省院内制剂,批号:08102305)治疗,西药组21例,采用二甲双胍(格华止,上海施贵宝药业公司)治疗,针药结合组28例,采用经验方灵术颗粒联合穴位埋线治疗。治疗3个月为一疗程。评价治疗前后主要临床症状、体征改善情况;以及治疗前后体重、BMI、腰围、臀围、WHR,多毛、痤疮评分、BBT、治疗前后性激素、GLU、INS、HOMA—IR、TG、Tc、HDL—C、LDL—C、ApoA、ApoB等疗效判定指标的改善情况。以及治疗前后检测一般安全性项目,及记录不良反应的发生。研究结论1.三组治疗均可以改善PCOS患者体内内分泌状况、在降低T水平上三组疗效无显著差异,西药组和针药结合组还可降低LH/FSH。2.三组治疗均可改善PCOS患者体重指数、腰围、臀围,针药结合组治疗后体重、腰围、臀围下降最为明显,西药组和中药组组间疗效相当。3.三组治疗均可改善PCOS患者IR,针药结合组与西药组在改善HOMA-IR方面的疗效优于单纯中药组,而西药组与针药结合组在改善HOMA—IR方面的疗效无统计学意义。4.针药结合组可改善PCOS患者的血脂情况,在疗效上优于中药组和西药组。5.三组治疗均可改善PCOS患者中医症状量化评分,中药组和针药结合组在改善中医症状方面疗效优于西药组。6.根据本研究结果,我们推测补肾健脾、化痰祛瘀法灵术颗粒以及灵术颗粒联合穴位埋线治疗PCOS的机理可能是通过降低T水平,改善胰岛素抵抗,降低患者体重,而起到调节内分泌的作用,具有多靶点、多方面整体调节下丘脑-垂体-卵巢轴的功能,从而达到促进卵泡发育和排卵的作用,其中降低体质量可能起到关键作用。7.根据上述客观研究结果,我们认为灵术颗粒,灵术颗粒联合穴位埋线是治疗PCOS合并IR患者的有效治疗方法。它可以明显降低体重、腰围、臀围,可以降低患者T水平,使患者月经规则、恢复排卵,且使部分不孕患者受孕,可通过降低T治疗高雄激素血症,改善座疮:可以降低FINS、HOMA-IR而改善胰岛素抵抗及因胰岛素抵抗引起的代偿性高胰岛素血症;针药结合组还可以改善血脂代谢情况。根据组间疗效差异比较,我们认为灵术颗粒联合穴位埋线在治疗PCOS并IR患者中起协同作用,疗效优于单纯中药治疗或单纯西药治疗。8.根据上述客观研究结果,我们认为灵术颗粒联合穴位埋线可以通过降低体质量,改善胰岛素抵抗,改善血脂代谢情况,在某种程度上可降低PCOS的远期并发症如糖尿病、高血脂和心血管等疾病的风险。更多还原

【Abstract】 BackgroundPolycystic ovary syndrome(PCOS) is a common endocrine syndrome of childbearing age women.Its incidence rate is as high as 5%to 10%,50%of which is caused by fatness,and 50%to 70%of them is caused by insulin resistance,which is a majority part in patients.Too much insulin acting on the corresponding receptor in the ovary will cause obstacles in follicular development and maturity and there won’t any advanced follicles.This will thus lead to anovulation and infertility.In that case,the symptoms,such as rare menstruation,amenorrhea,acne,hirsutism,obesity,infertility and so on will emerge.At present,it is considered that insulin resistance and hyperinsulinemia play a key role in the pathogenesis of polycystic ovary syndrome.Insulin resistance is also a high risk factor for many clinical diseases.It may increase the incidence ratio of diabetes,cardiovascular disease and endometrial cancer and has long future harm.Hence,it is very important to explore and find an effective treatment method for PCOS and IR with fewer side effects,which is also effectively preventive to future complications.Based on the existing treatises from former researchers and the long time clinical experiences accumulated by herself,TCM professor of our hospital Li Liyun,who is a provincial veteran,put forward the conclusion that the pathogenesis of polycystic ovary syndrome is basically in kidney deficiency and apparently in blood stasis and sputum obstacle.It is a deficiency-excess complication.So the method is tonifying the kidney,smoothing the sputum and invigorating the blood circulation to cure PCOS.She has established an experienced prescription and made the preparations,Necromancy Particle and Shenshi Capsule.Previous research has proved that these medicines do have healing effect onto the treatment of PCOS.Acupoint catgut embedding is a green acupuncture treatment rising in recent years,which is characterized by simplicity and cheapness.This treatment has a certain achievement on the treatment and research for obese patients.It is rare to find some reports on the clinical healing effect,action principle of TCM combined with acupoint catgut embedding therapy for curing PCOS,and the intervening effect of this treatment to the risk factor IR, obesity and blood fat related to PCOS long future complication.The evaluation standard o the healing effect is also different with each other.There is an obvious lack of systematic and normative research.So according to the present TCM research status of PCOS and the limitation of Western Medicine,we are planning to establish a TCM and acupoint catgut embedding combined method to see whether this combined treatment method can play an important role on intervening and curing PCOS and the high risk factors of its long future complication with the benefit of the good treatment effect of acupoint catgut embedding for obesity and the experienced prescription of Necromancy Particle from professor Li Liyun for curing PCOS.ObjectivesThrough comparing the clinical healing effect difference for PCOS between the Necromancy Particle from Professor Li Liyun,the most common medicine metformin for curing PCOS and IR in Western Medicine and the Necromancy Particle and acupoint catgut embedding combined treatment as well as observing improvement of menstruation,ovulation,body mass,reproductive endocrinology, insulin resistance,lipids,etc,this study is aiming at making objective evaluation to the clinical healing effects of Necromancy Particle and Necromancy Particle and acupoint catgut embedding combined treatment for PCOS and exploring the possible action mechanism in order to lay the foundation for the treatment method which has high efficiency and less side for curing PCOS and can also excellently prevent its long future complication.MethodThis study adopts forward looking clinical experiment research,chooses 77 PCOS and IR patients who went to Guangdong TCM Hospital to see gynecologic doctors during the time from February 2008 to February 2009 and are conforming to the diagnosis and adopting standard and divides them into three groups, TCM treatment group,Western Medicine treatment group and injection and medicine combined group.TCM treatment group has 28 patients and they are treated with the experienced prescription Necromancy Particle(domestic preparation,batch number:08102305).Western Medicine treatment group has 21 patients and they are treated with metformin(made in Shanghai).Injection and Medicine combined group has 28 patients and they are treated with Necromancy Particle and acupoint catgut embedding therapy,three months for each treatment period.This study evaluates the improvement situation of clinical symptoms and signs before and after the treatment,as well as the improvement situation of weight,BMI,waistline,hipline,WHR,hirsutism,acne scores,BBT,sex hormones before and after treatment,GLU,INS,HOMA-IR,TG, Tc,HDL-C,LDL-C,ApoA,ApoB and other indicators to determine efficacy, examines the general safety items before and after the treatment and records the occurrence of adverse reactions.Conclusion1.The treatment of all of the three groups can improve the endocrine status of PCOS patients.There is no significant difference with T level lowering between the three groups.The Western Medicine treatment group and injection and medicine combined group can also lower LH/FSH.2.The treatment of all of the three groups can improve the weight index, waistline and hipline of PCOS patients.The weight,waistline and hipline loss is the most significant in injection and medicine combined group after the treatment.That of the Western Medicine treatment group and TCM treatment group is almost the same.3.The treatment of all of the three groups can improve the IR of PCOS patients. The treatment of injection and medicine combined group and Western Medicine group has a better effect on HOMA-IR improvement than that of the TCM treatment group.There is no statistic importance to compare the HOMA-IR improvement effect of the Western Medicine group with that of the injection and medicine combined group.4.Blood fat status can be improved in injection and medicine combined group. Its effect is better than that of the TCM group and Western Medicine group. 5.The treatment of all of the three groups can improve the quantitative scores of TCM symptoms of PCOS patients.The TCM group and injection and medicine combined group have a better effect than the Western Medicine group.6.According to the results of this study,we suppose that the action principle of Necromancy Particle which is used to tonify the kidney,strengthen the spleen,smooth the sputum and remove obstacle,and Necromancy Particle and acupoint catgut embedding combined therapy for PCOS is to regulate the endocrine by lowering T level,improving insulin resistance and lowering the weight of patients.It has the function of regulating hypothalamus-pituitary -ovarian axis with multiple targets and overall aspect so as to achieve the promotion of follicular development and ovulation,Lowering the body mass may play a key role for that.7.Based on above objective results,we think the Necromancy Particle and acupoint catgut embedding combined treatment is an effective treatment method for curing PCOS and IR.It can significantly lower weight,waistline,hipline, and T level,regulate menstruation,restore ovulation,make some patients with infertility become pregnant,cure hyperprolanemia by lowering T,improve acne, and improve insulin resistance and vicarious hyperinsulinemia caused by insulin resistance by lowering FINS and HOMA-IR.injection and medicine combined treatment can also improve the blood fat metabolism status.According to the curative effect differences between the groups,we think the Necromancy Particle and acupoint catgut embedding combined treatment has a synergy effect in the treatment of PCOS and IR patients.It is better than single TCM treatment or Western Medicine treatment.8.According to the objective findings,we believe that the Necromancy Particle and acupoint catgut embedding combined treatment,through lowering the body mass,improving the insulin resistance and improving the blood fat metabolism status,can lower in a way the risk of PCOS long future complications,such as diabetes,high blood cholesterol,angiocardiopathy and so on.更多还原