摘要
目的 探讨miRNA-320及其靶基因内皮素-1与多囊卵巢综合征(PCOS)易感性及临床特点的关系。方法 选择2017年4月-2019年4月在重庆三峡中心医院妇科门诊就诊的75例PCOS患者为研究组,再根据稳态模型评估-胰岛素抵抗指数(HOMA-IR)分为非IR-PCOS组(HOMA-IR<2.11,n=40)和IR-PCOS组(HOMA-IR>2.11,n=35),选择同期门诊就诊的健康女性40名为对照组。采用自动生化分析仪测定血清生化指标,阴道超声评估卵巢体积和窦卵泡计数,多毛症Ferriman-Gallwey评分标准评估多毛症得分,ELISA测定血清内皮素-1、空腹血清胰岛素、卵泡刺激素(FSH)、黄体生成素(LH)、总睾酮水平,RT-PCR测定血清miRNA-320表达水平。符合正态分布的计量资料比较采用两独立样本t检验或单因素方差分析,相关性分析采用Pearson相关性分析,多变量分析采用线性回归分析和二元非条件logistic回归分析。结果 与对照组相比,PCOS组血清miRNA-320表达水平显著降低(t=3.170,P<0.05),血清内皮素-1水平显著升高(t=5.483,P<0.05)。与非IR-PCOS组相比,IR-PCOS组血清miRNA-320表达水平显著降低(t=-2.864,P<0.05),血清内皮素-1水平显著升高(t=2.513,P<0.05)。PCOS患者血清miRNA-320表达水平与多毛症得分、卵巢体积、窦卵泡计数、甘油三酯、空腹胰岛素、HOMA-IR、LH等呈负相关(r=-0.521^-0.270,P均<0.05),与稳态模型评估-β细胞功能指数(HOMA-β)呈正相关(r=0.022,P<0.05)。多毛症得分和HOMA-IR是PCOS患者血清miRNA-320水平的主要影响因子,miRNA-320表达水平为PCOS的独立危险因素(OR=4.356,95%CI:2.442~11.067,P<0.001)。血清miRNA-320预测PCOS的最佳截点为0.743,曲线下面积为0.816(95%CI:0.788~0.935,P<0.001),敏感性为80%,特异性为97.5%;血清内皮素-1预测PCOS的最佳截点为5.66 ng/L,曲线下面积为0.822(95%CI:0.804~0.959,P<0.001),敏感性为91.7%,特异性为99.3%。结论 PCOS患者血清miRNA-320表达水平显著降低,并负反馈调节内皮素-1的水平。miRNA-320与PCOS患者多毛症得分、卵巢体积、窦卵泡计数、甘油三酯、空腹胰岛素、HOMA-IR、HOMA-β、LH等呈负相关,诊断PCOS的特异性高,可作为PCOS的无创诊断生物标志物。
Objective To investigate the relationship between miRNA-320,its target gene endothelin-1 and the susceptibility and clinical features of polycystic ovary syndrome(PCOS).Methods A total of seventy-five patients with PCOS who were admitted to the Department of Gynecology of Chongqing Three Gorges Central Hospital from April 2017 to April 2019 were selected as study group.According to homeostasis model assessment of insulin resistance index(HOMA-IR),patients with PCOS were divided into non-IR-PCOS group(HOMA-IR<2.11,n=40)and IR-PCOS group(HOMA-IR>2.11,n=35).Another 40 healthy women of outpatient in the same period were selected as control group.Automatic biochemical analyzer was used to measure serum biochemical indicators,vaginal ultrasound was used to evaluate ovarian volume and sinus follicle number,and hirsutism Ferriman-Gallwey scoring standard was used to evaluate hirsutism score.ELISA was used to measure serum level of endothelin-1,fasting insulin,follicle stimulation hormone(FSH),luteinizing hormone(LH),and total testosterone.The expression of miRNA-320 in serum was determined by RT-PCR.Measurement data that fit the normal distribution were compared using two independent samples t test or one-way ANOVA,correlation analysis was performed using Pearson correlation analysis,and multivariate analysis was performed using linear regression analysis and binary unconditional logistic regression analysis.Results Compared with control group,the expression of serum miRNA-320 was significantly decreased in PCOS group(t=3.170,P<0.05),and serum endothelin-1 level was significantly increased(t=5.483,P<0.05).Compared with non-IR-PCOS group,the level of serum miRNA-320 was significantly decreased(t=-2.864,P<0.05),and serum endothelin-1 level was significantly increased(t=2.513,P<0.05)in IR-PCOS group.Expression of serum miRNA-320 in patients with PCOS were significantly and negatively correlated with hirsutism score,ovarian volume,sinus follicle count,triglycerides,fasting insulin,HOMA-IR,LH(r=-0.521--0.270,all P<0.05),but positive correlated with homeostasis model assessment ofβcell function index(HOMA-β,r=0.022,P<0.05).The hirsutism score and HOMA-IR were the main factors affecting serum miRNA-320 level in patients with PCOS.The expression of miRNA-320 was an independent risk factor of PCOS(OR=4.356,95%CI:2.442-11.067,P<0.001).The optimal cutoff value of serum miRNA-320 for predicting PCOS was 0.7429,with the area under the curve was 0.816(95%CI:0.788-0.935,P<0.001),the sensitivity was 80%,and the specificity was 97.5%.The optimal cut-off value of serum endothelin-1 for predicting PCOS was 5.66 ng/L,with the area under the curve was 0.822(95%CI:0.804-0.959,P<0.001),the sensitivity was 91.7%,and the specificity was 99.3%.Conclusions Expression of serum miRNA-320 is significantly reduced in patients with PCOS,and negatively regulates endothelin-1 level.MiRNA-320 is negatively correlated with hirsutism score,ovarian volume,sinus follicle count,triglyceride,fasting insulin,HOMA-IR,HOMA-β,and LH in patients with PCOS.The specificity of miRNA-320 is high,therefore can be used as non-invasive diagnostic biomarker of PCOS.
作者
牟靖
谈宗国
吴萍
Mou Jing;Tan Zongguo;Wu Ping(Department of Gynecology,Chongqing Three Gorges Central Hospital,Wanzhou 404100,China)
出处
《国际内分泌代谢杂志》
2020年第2期87-92,共6页
International Journal of Endocrinology and Metabolism
作者简介
通信作者:吴萍,Email:1961562648@qq.com。
