【作者】 王莉；

【导师】 尹利荣；

【作者基本信息】 天津医科大学 ， 妇产科学（专业学位）， 2013， 硕士

【摘要】 目的：本研究通过对肥胖型与非肥胖型多囊卵巢综合征(PCOS)患者进行流行病学资料比较,分析肥胖与非肥胖型PCOS患者疾病发生的相关因素。通过测定肥胖与非肥胖型PCOS患者血清胃促生长素(Ghrelin)与肥胖抑制素(Obestatin)浓度,及二甲双胍规律治疗四个月后血清Ghrelin与Obestatin浓度的变化,探讨肥胖与非肥胖型PCOS患者的发病机制是否存在差异,从而更全面、深入的认识疾病,为进一步明确其发病机制及疾病诊疗提供理论依据。方法：选取2011年6月——2011年12月在天津医科大学第二医院妇科门诊符合诊断标准的PCOS患者60例,以体质指数(BMI)为标准,将60例PCOS患者分为肥胖组(BMI≥25kg/m2)30例和非肥胖组(BMI＜25kg/m2)30例,以30例同期月经正常的输卵管因素或男方因素就诊的不孕患者为对照组。记录其年龄、月经情况、婚育史、有无糖尿病家族史、每周运动量、有无心理问题等,对统计结果进行分析。3组患者均采用全自动化学发光法测定血清生殖激素、空腹血糖(FBG)和空腹胰岛素(FIN)水平；采用酶联免疫吸附试验(ELISA)测定血清Ghrelin与Obestatin浓度。采用单向方差分析(one-way ANOVA)法比较各组间各指标的差异；并运用Pearson相关分析血清Ghrelin与Obestatin水平与各生化代谢指标的相关性。本次研究中,肥胖组有26例、非肥胖组有10例伴有胰岛素抵抗(IR)的PCOS患者,两组中伴有IR者均给予二甲双胍500mgTid规律治疗四个月后,随访患者一般情况及代谢指标变化,并采用ELISA法测定治疗后两组血清Ghrelin与Obestatin浓度,采用配对样本t检验法比较治疗前后血清Ghrelin与Obestatin水平变化情况。结果：(1)问卷调查表数据单因素logistic回归分析显示,糖尿病家族史、心理问题与肥胖组PCOS发生有统计学意义,但与非肥胖组PCOS发生无统计学意义；其他个人生活习惯(如吸烟、酗酒、偏好甜食、运动)及生育情况与肥胖及非肥胖PCOS发生均无统计学意义。流行病学研究发现,肥胖型PCOS患者较非肥胖型月经周期延长或闭经的患病率更高,而非肥胖型PCOS患者较肥胖型月经淋漓的患病率高。(2)治疗前血清Ghrelin与Obestatin水平：肥胖组、非肥胖组、对照组3组均检测到血清Ghrelin与Obestatin;肥胖组血清Ghrelin与Obestatin水平较非肥胖组及对照组均显著下降,差异有统计学意义(P<0.05)；而非肥胖组与对照组比较,差异无统计学意义(P>0.05)。(3)治疗前血清Ghrelin/Obestatin比较：肥胖组血清Ghrelin/Obestatin明显高于非肥胖组及对照组(P<0.05),而非肥胖组与对照组比较无明显差异(P>0.05)。(4)血清Ghrelin水平与各生化代谢指标的相关性：肥胖组血清Ghrelin水平与FIN、HOMA-IR呈负相关；非肥胖组血清Ghrelin水平与LH、LH/FSH、睾酮呈负相关。(5)血清Obestatin水平与各生化代谢指标的相关性：肥胖组血清Obestatin水平与FIN、 HOMA-IR呈负相关；非肥胖组血清Obestatin水平与LH、LH/FSH、睾酮呈负相关。(6)治疗后PCOS患者血清Ghrelin、Obestatin、Ghrelin/Obestatin水平变化：肥胖组PCOS患者血清Ghrelin、Obestatin水平明显升高,差异有统计学意义(P<0.05),而非肥胖组与治疗前相比无明显差异(P>0.05)。肥胖组PCOS患者Ghrelin/Obestatin水平较治疗前下降明显(P<0.05),非肥胖组无明显变化(P>0.05)。(7)治疗后肥胖组PCOS患者BMI、FIN、HOMA-IR较治疗前明显下降(P<0.05),而FBG较治疗前下降不明显,非肥胖组患者BMI、FBG、FIN、 HOMA-IR与治疗前相比均无明显差异(P>0.05)。结论：肥胖型PCOS患者发病机制以代谢紊乱为主,非肥胖型PCOS患者发病机制以下丘脑-垂体-卵巢轴功能障碍为主。采用二甲双胍治疗可以改善肥胖型PCOS患者代谢紊乱的状态,使血清Ghrelin与Obestatin水平升高。血清Ghrelin与Obestatin水平的变化与肥胖型PCOS发病密切相关。机体Ghrelin与Obestatin分泌紊乱导致IR可能是肥胖型PCOS患者的发病机制之一。更多还原

【Abstract】 Objective:According to comparing epidemiological data of obese and non-obese patients with polycystic ovarian syndrome(PCOS),we analysis the relevant factors of disease in patients with PCOS.By determining the concentration of serum Ghrelin、Obestatin in obese and non-obese patients with PCOS and the change after metformin treatment for4months, to investigate if there is a difference in obese and non-obese PCOS patients, to a more comprehensive and in-depth understanding of disease.so that to provide theoretical basis for disease diagnosis and treatment.Method:Total of90women were enrolled in the research who attended gynecology division of outpatient to the second hospital of Tianjin medical university from June2011to December2011.Body mass index(BMI) as a standard,60PCOS patients were divided into two groups:30cases in obese group(BMI>25kg/m2)and30cases in non-obese group(BMI＜25kg/m2),30infertile cases in the same period of regular menstruation with tubal or man factor as control group. The questionnaire content mainly includes age、menstrual history、pregnancies、with or without family history of diabetes and psychological problems and so on. The data was analyzed by logistic statistics. Ovarian sexual hormone and Sugar metabolism experiment were measured by completely automatic chemiluminescence method. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of serum Ghrelin and Obestatin. The indexes were compared by one-way ANOVA.The correlation between Ghrelin、 Obestatin and biological metabolic index was analyzed by simple correlation analysis. In this study,26cases in obese group and10cases in non-obese group with insulin resistance (IR), after metformin500mg Tid treatment for4months,follow-up of patients with general condition and metabolism index changes, and detect serum levels of Ghrelin and Obestatin using ELISA.Paired sample T test compare serum Ghrelin and Obestatin levels before and after treatment.Results:(1) The questionnaire data single factor logistic regression analysis showed that family history of diabetes, psychological problems had a certain statistical relationship with the occurrence of obese PCOS patients, but had no statistical relationship with non-obese PCOS patients; Other personal habits such as smoking, drinking, preference for sweets, sports and its fertility had no statistical significance with obese and non-obese PCOS. Epidemiological studies have found that obese PCOS patients have extended menstrual cycle or higher amenorrhea rates, non-obese PCOS patients’menstrual dripping wet incidence is higher.(2)Obese and non-obese group, control group were detected serum Ghrelin and Obestatin; Obese group serum Ghrelin and Obestatin levels were significantly lower compared with non-obese group and control group(P<0.05); other than there was no statistically significant difference between non-obese group and control group(P>0.05).(3)The level of Ghrelin/Obestatin in obese group was obviously higher than that in non-obese group (P＜0.05), the non-obese group and control group have no significant difference(P>0.05).(4)In obese group,serum Ghrelin level negatively correlated with FIN, HOMA-IR,in on-obese group,serum Ghrelin level showed a negative correlation with LH, LH/FSH and T.(5) The correlation of serum Obestatin is similar with Ghrelin.(6)After treatment,obese PCOS patients’serum Ghrelin、Obestatin levels increased significantly,the difference was statistically significant (P＜0.05), rather than the non-obese group has no significant difference(P>0.05).Obese PCOS patients’ Ghrelin/Obestatin levels decreased significantly compared with before(P<0.05), non-obese group has no significant change(P>0.05).(7)After treatment,obese patients’BMI、FIN、HOMA-IR significantly decreased than before(P<0.05), while FBG is not obvious, non obese patients’BMI、FBG、FIN、HOMA-IR had no obvious difference compared with before (P>0.05).Conclusions:The pathogenesis of obese PCOS patients is given priority to metabolic disorders,however the pathogenesis of non-obese PCOS patients were mainly because of hypothalamus-pituitary-ovarian axis dysfunction. Metformin therapy can improve obese PCOS patients’state of metabolic disorder, making serum Ghrelin and Obestatin levels increase. The secretion disorder of serum Ghrelin and Obestatin is closely related to the disease of obese PCOS. Ghrelin and Obestatin secretion disorder lead to IR,which may be one of the pathogenesis of obese PCOS.更多还原