本文選題：循環(huán)microRNA + miR-29a-3p��； 參考：《浙江大學(xué)》2015年碩士論文

【摘要】：[目的和背景] 代謝綜合征(metabolic syndrome,MetS)是中心性肥胖、糖代謝異常(糖尿病或糖調(diào)節(jié)受損)、高血壓和血脂異常等多種疾病或危險因素在個體聚集的一組臨床征候群。目前認(rèn)為其病理生理基礎(chǔ)可能是胰島素抵抗,但具體機制仍不確切。近年來,關(guān)于microRNA(簡稱miRNA)的發(fā)現(xiàn)和研究異軍突起,miRNA被證實參與和調(diào)節(jié)人類生理病理的多個環(huán)節(jié)�，F(xiàn)已有多項證據(jù)表明,循環(huán)miRNAs可能參與和影響糖脂代謝。本課題通過測定miRNA-29a-3p(以下簡稱miR-29a-3p)在代謝綜合征人群尿液中的表達量,觀察miR-29a-3p與各代謝組分的相關(guān)性,評估其患病風(fēng)險和診斷價值,希望能給代謝綜合征的診斷和治療帶來全新的思路和方法。 [方法] 將代謝綜合征患者及正常對照組共8例血清樣本進行了基于377個miRNAs探針的TaqMan MicroRNA芯片檢測,發(fā)現(xiàn)11個異常表達的miRNAs,其中7個為高表達,4個為低表達。本實驗選取其中高表達的miR-29a-3p作為研究對象,運用qRT-PCR技術(shù)在40例MetS及40例非MetS人群的尿液樣本中進行了驗證,通過t檢驗比較了兩組尿液miR-29a-3p的表達差異,并進一步運用Spearson相關(guān),多元逐步線性回歸,多元logistics回歸分析,ROC曲線等統(tǒng)計學(xué)方法對miR-29a-3p與各代謝亞組分進行相關(guān)性、患病風(fēng)險和診斷價值的分析。 [結(jié)果] TaqMan MicroRNA芯片檢測結(jié)果顯示代謝綜合征人群存在11個異常表達的miRNAs,其中有7個為高表達,分別是miR-20a-3p、miR-143a-3p、miR-365a-3p、 miR-22a-5p、miR-71a-5p、miR-29a-3p、miR-99a-5p、進一步對其中miR-29a-3p行qRT-PCR驗證,MetS組尿液miR-29a-3p的表達水平比非MetS組顯著升高(p0.001)；多元逐步線性回歸結(jié)果顯示尿液miR-29a-3p與空腹胰島素(beta=0.561, p0.001)、高密度脂蛋白(beta=0.242,p0.001)和BMI(beta=-0.141,p=0.025)成獨立相關(guān)。將尿液miR-29a-3p的qRT-PCR檢測所得Ct值計算相對濃度后進行二分組(分組界值為0.96),并控制年齡、性別、吸煙和飲酒因素,結(jié)果發(fā)現(xiàn)相對濃度大于0.96組,其MetS的患病風(fēng)險率是濃度小于0.96組的4.01倍(95%CI:1.22-13.12; p=0.022)。ROC曲線結(jié)果提示：尿液miR-29a-3p的表達水平對MetS具有一定診斷價值(AUC:0.776,P=0.001;95%CI:0.603-0.829),其診斷敏感性77.5%,特異性60%。 [結(jié)論] 尿液miR-29a-3p在MetS人群中相比非MetS人群其表達顯著增高,它可能通過促糖脂代謝異常來介導(dǎo)MetS的發(fā)生。尿液miR-29a-3p表達水平對MetS具有一定的診斷價值,有望成為新的分子診斷標(biāo)志物。這為進一步研究miR-29a-3p介導(dǎo)MetS發(fā)生的機制和生物學(xué)行為提供理論依據(jù),為MetS的靶向治療提供全新思路。
[Abstract]:[purpose and background] Metabolic syndrome (MS) is a group of clinical symptoms of central obesity, abnormal glucose metabolism (diabetes mellitus or impaired glucose regulation, hypertension and dyslipidemia). It is believed that insulin resistance may be the pathophysiological basis of insulin resistance, but the mechanism is still unclear. In recent years, the discovery and research of microRNAs (miRNAs) have been proved to be involved in and regulate human physiology and pathology. There is evidence that circulating miRNAs may be involved in and affect glucose and lipid metabolism. In this study, we measured the expression of miRNA-29a-3p (miR-29a-3p) in the urine of patients with metabolic syndrome, observed the correlation between miRNA-29a-3pand various metabolites, and evaluated the risk and diagnostic value of miRNA-29a-3p. We hope to bring new ideas and methods to the diagnosis and treatment of metabolic syndrome. [methods] A total of 8 serum samples from patients with metabolic syndrome and normal control were detected by TaqMan MicroRNA microarray based on 377 miRNAs probes. 11 abnormal expression of miRNas were found, including 7 high expression and 4 low expression. In this experiment, the high expression of miR-29a-3p was selected as the research object, and the urine samples of 40 cases of MetS and 40 cases of non-MetS were tested by qRT-PCR technique. The difference of the expression of miR-29a-3p in urine between the two groups was compared by t test, and Spearson correlation was used further. Multivariate stepwise linear regression and multivariate logistics regression analysis were used to analyze the correlation between miR-29a-3p and various metabolic subcomponents, the risk of disease and the diagnostic value. [results] The results of TaqMan MicroRNA microarray analysis showed that there were 11 abnormal expression of miRNas in metabolic syndrome population, 7 of which were overexpression. They were miR-20a-143a-3pnmiR-365a-3p, miR-22a-5pnmiR-71a-5pnmiR-29a-3pnmiR-99a-5p. the level of urinary miR-29a-3p in miR-29a-3p group was significantly higher than that in non-MetS group, and the multivariate stepwise linear regression analysis showed that urine miR-29a-3p was correlated with fasting insulin beta1 0.561, p0.001, high density lipoprotein beta1 0.242p0.001) and BMIbetaI 0.141p0. 025) respectively. The results of multiple stepwise linear regression showed that there was an independent correlation between urine miR-29a-3p and fasting insulin Beta 0.561, p0.001, high density lipoprotein beta1 0.242p0.001) and BMIbeta- 0.141 p0. 025). After calculating the relative concentration of Ct by qRT-PCR detection of urine miR-29a-3p, the group was divided into two groups (the threshold of the group was 0.96) and the factors of age, sex, smoking and drinking were controlled. The results showed that the relative concentration was greater than 0.96. The risk rate of MetS was 4.01 times of 95 CI: 1.22-13.12 in 0.96 group. The results of p=0.022).ROC curve indicated that the level of urinary miR-29a-3p expression had certain diagnostic value for MetS. The diagnostic sensitivity was 77.5% and specificity was 605%. [conclusion] The expression of miR-29a-3p in urine was significantly higher in MetS than in non-MetS, and it may mediate the occurrence of MetS by abnormal glucose and lipid metabolism. Urine miR-29a-3p expression level has certain diagnostic value to MetS, and it is expected to be a new molecular diagnostic marker. This provides a theoretical basis for the further study of the mechanism and biological behavior of MetS mediated by miR-29a-3p, and provides a new idea for the targeted treatment of MetS.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R589

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相關(guān)期刊論文 前2條

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本文編號：1915456