【摘要】：背景:非編碼微小RNAs(microRNAs,miRNAs)是非編碼單鏈小RNA,主要在轉(zhuǎn)錄后水平上調(diào)控基因表達(dá),異常miR-200家族(包括:miR-200a、b、c、miR-429及miR-141五位成員)表達(dá)與胰島素抵抗和糖尿病等發(fā)病密切相關(guān)。多囊卵巢綜合征(polycystic ovary syndrome,PCOS)是生育期婦女最常見的內(nèi)分泌疾病,它的主要特征是:卵巢多囊樣改變,稀發(fā)或無排卵,高雄激素和胰島素抵抗。而目前認(rèn)為胰島素抵抗和代償性高胰島素血癥在PCOS的發(fā)病中起著重要的作用。目的:探討PCOS患者顆粒細(xì)胞中miR-200家族的表達(dá),分析其與胰島素抵抗的關(guān)系及臨床意義,為PCOS的發(fā)病機制及未來的診斷治療方向提供理論依據(jù)。方法:收集2015年10月至2016年6月期間,于山東大學(xué)附屬生殖醫(yī)院就診患者,年齡35歲,控制性促排卵長方案,行體外受精一胚胎移植(invitro fertilization and embryo transfer,IVF-ET)或卵胞i}內(nèi)單精子注射(intracytoplasmic sperm injection,ICSI)助孕;PCOS患者共收集120例,計算胰島素抵抗指數(shù)(homeostasis model assessment-insulin resistance,HOMA-IR),將 HOMA-IR ≥2.57患者,設(shè)為PCOS胰島素抵抗組(P-IR組),共78例;而HOMA-IR2.57的患者為PCOS非胰島素抵抗組(P-NIR組),共42例;同時收集因男方因素或輸卵管因素助孕,且卵巢功能正�；颊�72例,作為對照組。采用定量即時聚合酶鏈鎖反應(yīng)(quantitative real time polymerase chain reaction,qRT-PCR)技術(shù),檢測三組患者顆粒細(xì)胞中miR-200家族成員的表達(dá)情況,分析miR-200家族表達(dá)和三組患者臨床資料及其相互關(guān)系。結(jié)果:(1)臨床資料分析:P-IR組中體重指數(shù)、空腹血糖、空腹血胰島素、HOMA-IR、HOMA-β、收縮壓及收縮壓、甘油三酯、低密度脂蛋白,高于P-NIR組和對照組患者(P均0.05),而高密度脂蛋白低于后兩者(P0.05);超重或肥胖、高血糖、高血壓、脂代謝紊亂及代謝綜合征的發(fā)病率都高于P-NIR組和對照組患者(P均0.05);且促排卵用藥時間比P-NIR組和正常對照患者(Control組)長(P=0.047,P=0.011),促排卵用藥劑量比PCOS非胰島素抵抗患者(P-NIR組)大(P=0.001)。(2)miR-200家族在患者卵巢顆粒細(xì)胞中表達(dá)情況:miR-200b在P-IR組患者表達(dá)量明顯高于P-NIR組和Control組(P均0.05);而P-NIR組和Control組中,miR-200b表達(dá)無差異(P均≥0.05)。miR-141在P-IR和P-NIR兩組患者中表達(dá)量均明顯高于Control組患者(P均0.05)。(3)miR-200家族相對表達(dá)量與臨床指標(biāo)的分析:在P-IR組中,miR-200b表達(dá)量與胰島素抵抗指數(shù)(HOMA-IR)呈正相關(guān)(r=0.532,P=0.002)。在P-NIR組中,miR-141與患者優(yōu)質(zhì)胚胎率正相關(guān)(r=0.576,P=O.001)。ROC曲線提示miR-141和miR-200c及二者聯(lián)合對PCOS的診斷有一定作用(AUC:0.736,0.632和0.717),而miR-141的診斷效能最優(yōu)。結(jié)論:PCOS胰島素抵抗患者高血壓等代謝方面遠(yuǎn)期并發(fā)癥的患病率較高,對胰島素抵抗治療在應(yīng)給予足夠重視。miR-200b高表達(dá)與PCOS胰島素抵抗正相關(guān),可能是PCOS患者出現(xiàn)胰島素抵抗的重要病理機制之一;miR-141在PCOS胰島素抵抗和非抵抗患者中均異常高表達(dá),提示miR-141可能還參與PCOS的發(fā)病,同時miR-141和PCOS非胰島素抵抗患者的優(yōu)質(zhì)胚胎率正相關(guān),提示miR-141的表達(dá)可能影響胚胎發(fā)育,同時對PCOS有一定的診斷價值。
[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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R711.75

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