血清miRNA-222在PCOS伴高胰岛素血症患者中的差异性表达及意义

发布时间：2018-05-08 20:44

本文选题：多囊卵巢综合征 + 微小RNA　；参考：《青岛大学》2017年硕士论文

【摘要】：背景:多囊卵巢综合征(PCOS)是生育期女性最常见的生殖内分泌代谢紊乱性疾病,以卵巢多囊表现、月经稀发或者闭经、不孕、肥胖为主要临床特征,并常伴有高雄激素血症、胰岛素抵抗(IR)、高胰岛素血症(HI)等内分泌紊乱的表现。除此以外,PCOS相关远期并发症,例如糖尿病、心血管疾病、子宫内膜病变、代谢综合征等影响着PCOS患者远期生活质量。胰岛素抵抗(IR)作为PCOS的主要内分泌特征,可能参与PCOS相关远期并发症,特别是糖尿病的发生。微小RNA(micro RNA,miRNA)是一类非编码RNA,其可在转录后水平负性调节靶基因的表达。目前的研究已表明miRNA不仅参与卵泡的发育成熟、甾体激素代谢等过程,而且发现PCOS患者miRNA的表达水平具有器官、组织及疾病相关特异性,这提示miRNA可能参与PCOS、IR相关的病理生理过程。近期的研究发现miRNA稳定存在于外周血及各种体液中,并且其表达水平与疾病密切相关,显示了体液中miRNA在疾病诊断、治疗及判断预后的潜能。目的:检测血清miRNA-222在PCOS伴高胰岛素血症患者与年龄、BMI相匹配健康女性的表达差异性以及口服二甲双胍对miRNA-222表达的影响,探讨miRNA-222与PCOS及IR的关系。方法:采用RT-PCR的方法检测PCOS伴高胰岛素血症患者(n=30)和年龄、BMI相匹配健康女性(对照组,n=30)血清中miRNA-222的表达;利用相关分析讨论miRNA-222与PCOS临床及生化指标的相关关系;应用二甲双胍(500mg,tid,连续4周)治疗,进一步检测并分析治疗前后(n=17)自身血清miRNA-222的表达变化。结果:PCOS伴高胰岛素血症患者血清miRNA-222的表达水平高于对照组,差别具有统计学意义(P0.05),ROC曲线下面积(AUC)为0.703;血清miRNA-222的表达与胰岛素水平呈正相关(R2=0.7462,P0.001);PCOS伴高胰岛素血症患者经二甲双胍治疗后miRNA-222表达水平较前下调,差别具有统计学意义(P0.05)。结论:血清miRNA-222在PCOS伴高胰岛素血症患者中表达显著上调,且与胰岛素水平正相关;口服二甲双胍下调PCOS患者血清miRNA-222表达。血清miRNA-222可能参与PCOS、IR和相关远期并发症的病理生理过程。意义:本研究显示,血清miRNA-222的表达水平在PCOS伴高胰岛素血症患者中显著升高,表明血清可以作为PCOS相关miRNA研究的标本来源,其相对于组织来讲更易获取,相对具有临床应用价值。研究还显示血清miRNA-222的表达与胰岛素水平正相关,提示血清miRNA-222可能参与胰岛素及糖类物质代谢,为PCOS在诊断、治疗和评估预后提供新的思路。
[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.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R711.75

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