男性不育患者精浆miR-551b水平变化及其临床价值  

Clinical Value of Seminal Plasma miR-551b in the Diagnosis of Male Infertility

作　　者：朱媛媛[1] 顾万建[2] 徐天[2] 邵永 王成 张春妮 ZHU Yuan- yuan 1a ,GU Wan -jian 1b ,XU Tian 1b ,SHAO Yong 2a ,WANG Cheng 2b ,ZHANG Chun-ni 2b(1a. Department of Science and Technology;1b. Department of Clinical Laboratory, Jiang su Province Hospital of TCM, Nanjing 210029, China; 2a. Reproductive Medical Center; 2b. Department of Clinical Laboratory, Nanjing General Hospital, Nanjing 210002, China)

机构地区：[1]江苏省中医院科技处,南京210029 [2]江苏省中医院检验科,南京210029 [3]南京总医院生殖医学中心,南京210002 [4]南京总医院检验科,南京210002

出　　处：《现代检验医学杂志》2018年第6期1-4,8,共5页Journal of Modern Laboratory Medicine

基　　金：国家自然科学基金资助项目(81401257);江苏省中医院院级创新发展基金(Y2018CX07)

摘　　要：目的检测和分析男性不育症患者精浆miR-551b水平变化,探讨其作为男性不育症辅助分子标志物的可能性。方法选取2008年11月～2015年3月在南京总医院生殖医学中心和江苏省中医院男科门诊确诊的92例男性不育症患者及同期招募的34例年龄匹配正常生育男性精液标本,记录患者及对照临床资料,测定患者及对照精液参数包括精子密度、精子活率、a级精子比例、a+b级精子比例及部分精浆生化指标α-糖苷、酸性磷酸酶、肉毒碱、果糖水平。实时荧光定量PCR技术(quantitative real-time PCR,qRT-PCR)检测和比较弱精症、非梗阻性无精症患者及正常生育男性精浆中miR-551b含量变化,统计分析精浆miR-551b临床价值及与精液参数、精浆生化指标相关性。结果 qRT-PCR结果显示,正常生育组精浆miR-551b水平为20.63(9.59,37.83)fmol/L,弱精症患者为62.29(25.22,101.43)fmol/L,较正常生育组显著升高(U=297.00);无精症患者精浆miR-551b水平为4.70(2.41,13.71)fmol/L,较正常生育组明显降低(U=356.00),差异均具有统计学意义(P<0.001)。受试者工作特征曲线(receiver operating characteristic curve,ROC)分析显示,精浆miR-551b区分弱精症、无精症患者与正常生育组的ROC曲线下面积(AUC ROC)分别为0.810(95%CI 0.718～0.902)和0.772(95%CI 0.667～0.878);鉴别弱精症和无精症患者的AUC ROC为0.932(95%CI 0.885～0.979)。Spearman秩相关性分析显示,男性不育患者精浆miR-551b水平与精子密度(r=0.735)、精子活率(r=0.643)、a级精子比例(r=0.672)、a+b级精子比例(r=0.682)及α-糖苷(r=0.375)呈正相关,差异均具有统计学意义(均P<0.05)。逐步多元线性回归结果显示,男性不育症患者精浆miR-551b水平与精子密度呈显著独立相关(β=0.618,P<0.001,校正r2=0.368)。逻辑回归分析显示,精浆miR-551b是弱精症[OR=24.889(95%CI 5.302～116.843),P<0.001]和无精症[OR=6.303(95%CI1.316～30.179),P=0.021]的潜在危险因素。结论男性�Objective To investigate the alteration pattern of seminal plasma miR-551b in infertile men and further evaluate the diagnostic potential of seminal plasma miR-551b as an auxiliary molecular marker for male infertility.Methods Semen samples were collected from 92 infertile men and 34 age-matched fertile controls in Nanjing General Hospital and Jiangsu Province Hospital of TCM between November 2008 and March 2015.Semen parameters including sperm density,motility rate,the ratio of grade a spermatozoon and grade a+b spermatozoon,as well as seminal plasma biochemical indexes such as alpha-glucosidase,acid phosphatase,carnitine and fructose were assessed.Quantitive Real-time PCR(qRT-PCR)assays were used to determine the concentrations of seminal plasma miR-551b in the patients with asthenozoospermia,non-obstructive azoospermia and fertile controls.Statistical analyses were performed to evaluate the clinical value of seminal plasma miR-551b for male infertility as well as to assess the clinical association between the levels of seminal plasma miR-551b and other semen and seminal plasma parameters.Results The seminal plasma levels of miR-551b in the asthenozoospermia group[62.29(25.22,101.43)fmol/L]were significantly higher than that in the fertile control[20.63(9.59,37.83)fmol/L](U=297.00,P<0.001),but with markedly lower concentration in the non-obstructive azoospermia group [4.70(2.41,13.71)fmol/L]as compared with the controls(U=356.00,P<0.001).ROC curve analysis showed that AUCs of miR-551b for discriminating asthenozoospermia and non-obstructive azoospermia were 0.810(95%CI 0.718～0.902)and 0.772(95% CI 0.667～0.878),respectively,and that the AUCs for differentiating asthenozoospermia and non-obstructive azoospermia was 0.932(95%CI 0.885～0.979).Spearman rank correlations analyses showed that the levels of seminal plasma miR-551b were significantly associated with sperm density(r=0.735),motility rate(r=0.643),the ratio of grade a spermatozoon(r=0.672),the ratio of grade a+b spermatozoon(r=0.682)and alpha-glucosid

关 键 词：微小核糖核酸-551b 男性不育症 精浆 弱精症 无精症 分子标志物 

分 类 号：R698.2[医药卫生—泌尿科学] R446.19[医药卫生—外科学]