多囊卵巢综合征患者颗粒细胞中microRNA-200家族的表达及临床意义
发布时间：2018-08-03 13:46
【摘要】：背景:非编码微小RNAs(microRNAs,miRNAs)是非编码单链小RNA,主要在转录后水平上调控基因表达,异常miR-200家族(包括:miR-200a、b、c、miR-429及miR-141五位成员)表达与胰岛素抵抗和糖尿病等发病密切相关。多囊卵巢综合征(polycystic ovary syndrome,PCOS)是生育期妇女最常见的内分泌疾病,它的主要特征是:卵巢多囊样改变,稀发或无排卵,高雄激素和胰岛素抵抗。而目前认为胰岛素抵抗和代偿性高胰岛素血症在PCOS的发病中起着重要的作用。目的:探讨PCOS患者颗粒细胞中miR-200家族的表达,分析其与胰岛素抵抗的关系及临床意义,为PCOS的发病机制及未来的诊断治疗方向提供理论依据。方法:收集2015年10月至2016年6月期间,于山东大学附属生殖医院就诊患者,年龄35岁,控制性促排卵长方案,行体外受精一胚胎移植(invitro fertilization and embryo transfer,IVF-ET)或卵胞i}内单精子注射(intracytoplasmic sperm injection,ICSI)助孕;PCOS患者共收集120例,计算胰岛素抵抗指数(homeostasis model assessment-insulin resistance,HOMA-IR),将 HOMA-IR ≥2.57患者,设为PCOS胰岛素抵抗组(P-IR组),共78例;而HOMA-IR2.57的患者为PCOS非胰岛素抵抗组(P-NIR组),共42例;同时收集因男方因素或输卵管因素助孕,且卵巢功能正常患者72例,作为对照组。采用定量即时聚合酶链锁反应(quantitative real time polymerase chain reaction,qRT-PCR)技术,检测三组患者颗粒细胞中miR-200家族成员的表达情况,分析miR-200家族表达和三组患者临床资料及其相互关系。结果:(1)临床资料分析:P-IR组中体重指数、空腹血糖、空腹血胰岛素、HOMA-IR、HOMA-β、收缩压及收缩压、甘油三酯、低密度脂蛋白,高于P-NIR组和对照组患者(P均0.05),而高密度脂蛋白低于后两者(P0.05);超重或肥胖、高血糖、高血压、脂代谢紊乱及代谢综合征的发病率都高于P-NIR组和对照组患者(P均0.05);且促排卵用药时间比P-NIR组和正常对照患者(Control组)长(P=0.047,P=0.011),促排卵用药剂量比PCOS非胰岛素抵抗患者(P-NIR组)大(P=0.001)。(2)miR-200家族在患者卵巢颗粒细胞中表达情况:miR-200b在P-IR组患者表达量明显高于P-NIR组和Control组(P均0.05);而P-NIR组和Control组中,miR-200b表达无差异(P均≥0.05)。miR-141在P-IR和P-NIR两组患者中表达量均明显高于Control组患者(P均0.05)。(3)miR-200家族相对表达量与临床指标的分析:在P-IR组中,miR-200b表达量与胰岛素抵抗指数(HOMA-IR)呈正相关(r=0.532,P=0.002)。在P-NIR组中,miR-141与患者优质胚胎率正相关(r=0.576,P=O.001)。ROC曲线提示miR-141和miR-200c及二者联合对PCOS的诊断有一定作用(AUC:0.736,0.632和0.717),而miR-141的诊断效能最优。结论:PCOS胰岛素抵抗患者高血压等代谢方面远期并发症的患病率较高,对胰岛素抵抗治疗在应给予足够重视。miR-200b高表达与PCOS胰岛素抵抗正相关,可能是PCOS患者出现胰岛素抵抗的重要病理机制之一;miR-141在PCOS胰岛素抵抗和非抵抗患者中均异常高表达,提示miR-141可能还参与PCOS的发病,同时miR-141和PCOS非胰岛素抵抗患者的优质胚胎率正相关,提示miR-141的表达可能影响胚胎发育,同时对PCOS有一定的诊断价值。
[Abstract]:Background: the non coding small RNAs (microRNAs, miRNAs) is a non coding single strand small RNA that mainly regulates gene expression at post transcriptional level. The expression of abnormal miR-200 family (including five members of miR-200a, B, C, miR-429 and miR-141) is closely related to the incidence of insulin resistance and diabetes. Polycystic ovary syndrome (polycystic ovary) is The most common endocrine disease of women in the childbearing period is characterized by polycystic changes of the ovary, dilute hair or anovulatory, hormone and insulin resistance in Kaohsiung. At present, insulin resistance and compensatory hyperinsulinemia play an important role in the pathogenesis of PCOS. Objective: To explore the expression of miR-200 family in granulosa cells of PCOS patients. The relationship and clinical significance of insulin resistance and its clinical significance were analyzed to provide a theoretical basis for the pathogenesis of PCOS and the future direction of diagnosis and treatment. Methods: from October 2015 to June 2016, the patients in the affiliated reproductive Hospital of Shandong University were aged 35 years old, control ovulation induction and embryo transfer (invitro ferti). Lization and embryo transfer, IVF-ET) or intracytoplasmic sperm injection (intracytoplasmic sperm injection, ICSI) were injected (intracytoplasmic sperm injection, ICSI); PCOS patients collected 120 cases, calculated insulin resistance index (homeostasis), and set up more than 2.57 patients, with 78 cases. OMA-IR2.57 patients were 42 cases of PCOS non insulin resistance group (group P-NIR), and 72 patients with normal ovarian function and normal ovarian function were collected at the same time as the control group. The quantitative real-time polymerase chain reaction (quantitative real time polymerase chain reaction, qRT-PCR) was used to detect the fine particle size in the three groups. The expression of miR-200 family members in the cell and the relationship between the miR-200 family expression and the clinical data of three groups of patients. Results: (1) clinical data analysis: body mass index (BMI), fasting blood glucose, fasting blood insulin, HOMA-IR, HOMA- beta, systolic and systolic pressure, triglyceride, low density lipoprotein in the P-IR group, higher than those in the P-NIR group and the control group ( P was 0.05), and high density lipoprotein was lower than that of the latter two (P0.05); the incidence of overweight or obesity, hyperglycemia, hypertension, lipid metabolism disorder and metabolic syndrome were higher than that of group P-NIR and control group (P 0.05), and the time of ovulation induction was longer than that of group P-NIR and normal control (Control group) (P=0.047, P=0.011), and the dosage of ovulation induction was more than PCOS. In patients with non insulin resistance (group P-NIR) (group P-NIR), (P=0.001). (2) the expression of the miR-200 family in the ovarian granulosa cells: the expression of miR-200b in the P-IR group was significantly higher than that in the P-NIR group and the Control group (P 0.05), while in the P-NIR group and the Control group, the miR-200b expression was no difference (P is equal to 0.05). Significantly higher than the Control group (P 0.05). (3) the analysis of the relative expression and clinical indicators of the miR-200 family: in the P-IR group, the miR-200b expression was positively correlated with the insulin resistance index (HOMA-IR) (r=0.532, P=0.002). In the P-NIR group, miR-141 was positively correlated with the high quality embryo rate (r=0.576, P=O.001). The combination of the two has a certain role in the diagnosis of PCOS (AUC:0.736,0.632 and 0.717), and the diagnostic efficiency of miR-141 is the best. Conclusion: the prevalence rate of long-term complications in PCOS insulin resistance patients is higher, and the high expression of.MiR-200b in insulin resistance therapy should be positively correlated with PCOS insulin resistance, which may be P COS patients are one of the most important pathological mechanisms of insulin resistance; miR-141 is highly expressed in PCOS insulin resistance and non resistance patients, suggesting that miR-141 may also participate in the pathogenesis of PCOS, and the high quality embryo rate of miR-141 and PCOS non insulin resistance patients is positively correlated. It suggests that the expression of miR-141 may affect the development of embryos and at the same time to PC. OS has a certain diagnostic value.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R711.75
[Abstract]:Background: the non coding small RNAs (microRNAs, miRNAs) is a non coding single strand small RNA that mainly regulates gene expression at post transcriptional level. The expression of abnormal miR-200 family (including five members of miR-200a, B, C, miR-429 and miR-141) is closely related to the incidence of insulin resistance and diabetes. Polycystic ovary syndrome (polycystic ovary) is The most common endocrine disease of women in the childbearing period is characterized by polycystic changes of the ovary, dilute hair or anovulatory, hormone and insulin resistance in Kaohsiung. At present, insulin resistance and compensatory hyperinsulinemia play an important role in the pathogenesis of PCOS. Objective: To explore the expression of miR-200 family in granulosa cells of PCOS patients. The relationship and clinical significance of insulin resistance and its clinical significance were analyzed to provide a theoretical basis for the pathogenesis of PCOS and the future direction of diagnosis and treatment. Methods: from October 2015 to June 2016, the patients in the affiliated reproductive Hospital of Shandong University were aged 35 years old, control ovulation induction and embryo transfer (invitro ferti). Lization and embryo transfer, IVF-ET) or intracytoplasmic sperm injection (intracytoplasmic sperm injection, ICSI) were injected (intracytoplasmic sperm injection, ICSI); PCOS patients collected 120 cases, calculated insulin resistance index (homeostasis), and set up more than 2.57 patients, with 78 cases. OMA-IR2.57 patients were 42 cases of PCOS non insulin resistance group (group P-NIR), and 72 patients with normal ovarian function and normal ovarian function were collected at the same time as the control group. The quantitative real-time polymerase chain reaction (quantitative real time polymerase chain reaction, qRT-PCR) was used to detect the fine particle size in the three groups. The expression of miR-200 family members in the cell and the relationship between the miR-200 family expression and the clinical data of three groups of patients. Results: (1) clinical data analysis: body mass index (BMI), fasting blood glucose, fasting blood insulin, HOMA-IR, HOMA- beta, systolic and systolic pressure, triglyceride, low density lipoprotein in the P-IR group, higher than those in the P-NIR group and the control group ( P was 0.05), and high density lipoprotein was lower than that of the latter two (P0.05); the incidence of overweight or obesity, hyperglycemia, hypertension, lipid metabolism disorder and metabolic syndrome were higher than that of group P-NIR and control group (P 0.05), and the time of ovulation induction was longer than that of group P-NIR and normal control (Control group) (P=0.047, P=0.011), and the dosage of ovulation induction was more than PCOS. In patients with non insulin resistance (group P-NIR) (group P-NIR), (P=0.001). (2) the expression of the miR-200 family in the ovarian granulosa cells: the expression of miR-200b in the P-IR group was significantly higher than that in the P-NIR group and the Control group (P 0.05), while in the P-NIR group and the Control group, the miR-200b expression was no difference (P is equal to 0.05). Significantly higher than the Control group (P 0.05). (3) the analysis of the relative expression and clinical indicators of the miR-200 family: in the P-IR group, the miR-200b expression was positively correlated with the insulin resistance index (HOMA-IR) (r=0.532, P=0.002). In the P-NIR group, miR-141 was positively correlated with the high quality embryo rate (r=0.576, P=O.001). The combination of the two has a certain role in the diagnosis of PCOS (AUC:0.736,0.632 and 0.717), and the diagnostic efficiency of miR-141 is the best. Conclusion: the prevalence rate of long-term complications in PCOS insulin resistance patients is higher, and the high expression of.MiR-200b in insulin resistance therapy should be positively correlated with PCOS insulin resistance, which may be P COS patients are one of the most important pathological mechanisms of insulin resistance; miR-141 is highly expressed in PCOS insulin resistance and non resistance patients, suggesting that miR-141 may also participate in the pathogenesis of PCOS, and the high quality embryo rate of miR-141 and PCOS non insulin resistance patients is positively correlated. It suggests that the expression of miR-141 may affect the development of embryos and at the same time to PC. OS has a certain diagnostic value.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R711.75
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