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血清miRNA-222在PCOS伴高胰島素血癥患者中的差異性表達(dá)及意義

發(fā)布時間:2018-05-08 20:44

  本文選題:多囊卵巢綜合征 + 微小RNA ; 參考:《青島大學(xué)》2017年碩士論文


【摘要】:背景:多囊卵巢綜合征(PCOS)是生育期女性最常見的生殖內(nèi)分泌代謝紊亂性疾病,以卵巢多囊表現(xiàn)、月經(jīng)稀發(fā)或者閉經(jīng)、不孕、肥胖為主要臨床特征,并常伴有高雄激素血癥、胰島素抵抗(IR)、高胰島素血癥(HI)等內(nèi)分泌紊亂的表現(xiàn)。除此以外,PCOS相關(guān)遠(yuǎn)期并發(fā)癥,例如糖尿病、心血管疾病、子宮內(nèi)膜病變、代謝綜合征等影響著PCOS患者遠(yuǎn)期生活質(zhì)量。胰島素抵抗(IR)作為PCOS的主要內(nèi)分泌特征,可能參與PCOS相關(guān)遠(yuǎn)期并發(fā)癥,特別是糖尿病的發(fā)生。微小RNA(micro RNA,miRNA)是一類非編碼RNA,其可在轉(zhuǎn)錄后水平負(fù)性調(diào)節(jié)靶基因的表達(dá)。目前的研究已表明miRNA不僅參與卵泡的發(fā)育成熟、甾體激素代謝等過程,而且發(fā)現(xiàn)PCOS患者miRNA的表達(dá)水平具有器官、組織及疾病相關(guān)特異性,這提示miRNA可能參與PCOS、IR相關(guān)的病理生理過程。近期的研究發(fā)現(xiàn)miRNA穩(wěn)定存在于外周血及各種體液中,并且其表達(dá)水平與疾病密切相關(guān),顯示了體液中miRNA在疾病診斷、治療及判斷預(yù)后的潛能。目的:檢測血清miRNA-222在PCOS伴高胰島素血癥患者與年齡、BMI相匹配健康女性的表達(dá)差異性以及口服二甲雙胍對miRNA-222表達(dá)的影響,探討miRNA-222與PCOS及IR的關(guān)系。方法:采用RT-PCR的方法檢測PCOS伴高胰島素血癥患者(n=30)和年齡、BMI相匹配健康女性(對照組,n=30)血清中miRNA-222的表達(dá);利用相關(guān)分析討論miRNA-222與PCOS臨床及生化指標(biāo)的相關(guān)關(guān)系;應(yīng)用二甲雙胍(500mg,tid,連續(xù)4周)治療,進(jìn)一步檢測并分析治療前后(n=17)自身血清miRNA-222的表達(dá)變化。結(jié)果:PCOS伴高胰島素血癥患者血清miRNA-222的表達(dá)水平高于對照組,差別具有統(tǒng)計學(xué)意義(P0.05),ROC曲線下面積(AUC)為0.703;血清miRNA-222的表達(dá)與胰島素水平呈正相關(guān)(R2=0.7462,P0.001);PCOS伴高胰島素血癥患者經(jīng)二甲雙胍治療后miRNA-222表達(dá)水平較前下調(diào),差別具有統(tǒng)計學(xué)意義(P0.05)。結(jié)論:血清miRNA-222在PCOS伴高胰島素血癥患者中表達(dá)顯著上調(diào),且與胰島素水平正相關(guān);口服二甲雙胍下調(diào)PCOS患者血清miRNA-222表達(dá)。血清miRNA-222可能參與PCOS、IR和相關(guān)遠(yuǎn)期并發(fā)癥的病理生理過程。意義:本研究顯示,血清miRNA-222的表達(dá)水平在PCOS伴高胰島素血癥患者中顯著升高,表明血清可以作為PCOS相關(guān)miRNA研究的標(biāo)本來源,其相對于組織來講更易獲取,相對具有臨床應(yīng)用價值。研究還顯示血清miRNA-222的表達(dá)與胰島素水平正相關(guān),提示血清miRNA-222可能參與胰島素及糖類物質(zhì)代謝,為PCOS在診斷、治療和評估預(yù)后提供新的思路。
[Abstract]:Background: polycystic ovary syndrome (PCOS) is the most common disorder of reproductive endocrine and metabolism in women during reproductive period. It is characterized by ovarian polycystic manifestations, menorrhagia or amenorrhea, infertility, obesity, and often accompanied by hyperandrogenemia. Insulin resistance, hyperinsulinemia and other endocrine disorders. In addition, long-term complications such as diabetes, cardiovascular disease, endometrial disease and metabolic syndrome affect the long-term quality of life of PCOS patients. Insulin resistance (IRR), as the main endocrine feature of PCOS, may be involved in the long term complications associated with PCOS, especially diabetes mellitus. Small RNA(micro RNAs are a class of noncoding RNAs that negatively regulate the expression of target genes at post-transcriptional level. Recent studies have shown that miRNA is not only involved in follicular maturation and steroid hormone metabolism, but also has organ, tissue and disease-related specificity in the expression of miRNA in PCOS patients. This suggests that miRNA may be involved in PCOSIR related pathophysiological processes. Recent studies have found that miRNA exists stably in peripheral blood and all kinds of body fluids, and its expression level is closely related to disease, indicating the potential of miRNA in diagnosis, treatment and prognosis. Aim: to investigate the difference of serum miRNA-222 expression in PCOS patients with hyperinsulinemia and healthy women matched by age and age, and the effect of metformin on the expression of miRNA-222, and to explore the relationship between miRNA-222 and PCOS and IR. Methods: RT-PCR was used to detect the expression of miRNA-222 in serum of PCOS patients with hyperinsulinemia and matched healthy women (control group), and the correlation between miRNA-222 and clinical and biochemical indexes of PCOS was discussed by correlation analysis. Metformin 500 mg / d for 4 weeks was used to detect and analyze the changes of serum miRNA-222 expression before and after treatment. Results the expression of miRNA-222 in the patients with hyperinsulinemia was higher than that in the control group. The area under the curve of P0.05 was 0.703.The expression of serum miRNA-222 was positively correlated with the level of insulin in patients with hyperinsulinemia. The expression of miRNA-222 in patients with hyperinsulinemia was significantly lower than that in patients with hyperinsulinemia after metformin treatment, and the difference was statistically significant (P 0.05). Conclusion: the expression of serum miRNA-222 in PCOS patients with hyperinsulinemia is significantly up-regulated and positively correlated with insulin level, and metformin can down-regulate the expression of serum miRNA-222 in patients with PCOS. Serum miRNA-222 may be involved in the pathophysiological process of PCOSIR and related long-term complications. Significance: this study showed that the expression of serum miRNA-222 was significantly increased in patients with PCOS and hyperinsulinemia, suggesting that serum can be used as a sample source for PCOS related miRNA studies, and it is easier to obtain than tissue. It has relatively clinical application value. The study also showed that the expression of serum miRNA-222 was positively correlated with the level of insulin, suggesting that serum miRNA-222 may be involved in the metabolism of insulin and carbohydrates, which provides a new idea for the diagnosis, treatment and evaluation of prognosis of PCOS.
【學(xué)位授予單位】:青島大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R711.75

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

1 Hong Zheng;Jia-Yu Liu;Feng-Ju Song;Ke-Xin Chen;;Advances in circulating microRNAs as diagnostic and prognostic markers for ovarian cancer[J];Cancer Biology & Medicine;2013年03期

2 Lingfeng Meng;Liang Chen;Zhaoyong Li;Zheng-Xing Wu;Ge Shan;;Roles of MicroRNAs in the Caenorhabditis elegans Nervous System[J];Journal of Genetics and Genomics;2013年09期

3 Ying-Feng Wei;Guang-Ying Cui;Ping Ye;Jia-Ning Chen;Hong-Yan Diao;;MicroRNAs may solve the mystery of chronic hepatitis B virus infection[J];World Journal of Gastroenterology;2013年30期



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