中枢性性早熟女童血清miR-125b与维生素D联合检测的临床意义研究

背景　下丘脑-垂体-性腺轴过早激活是中枢性性早熟（CPP）的主要发生机制，但其激活的机制尚不明确。微小核糖核酸可能参与了性早熟的发生发展。目的　分析CPP女童血清miR-125b与维生素D、激素指标的关系，并分析血清miR-125b与维生素D联合检测的临床意义。方法　收集2013—2016年每年的7—9月在南方医科大学附属中山博爱医院就诊的102例CPP女童（CPP女童组）及同时期年龄匹配的体检健康女童102例（健康女童组），记录两组的临床指标〔年龄、身高、体质量、体质指数（BMI）、乳房发育年龄、卵巢体积、骨龄、骨龄与年龄差、体质量标准差分数（WSDS）、身高标准差分数（HSDS）、体质指数标准差分数（BMI SDS）〕、乳腺Tanner分期；采用实时荧光定量PCR检测血清miR-125b；采用化学发光法检测血清25-羟基维生素D（25-OH-D）及激素指标（游离甲状腺素、促甲状腺素、雌二醇、泌乳素、黄体生成素、卵泡刺激素）。结果　CPP女童组血清miR-125b高于健康女童组（P<0.05）。CPP女童组血清miR-125b与25-OH-D呈负相关（r=-0.809 5，P<0.01）。将CPP女童分为miR-125b高表达亚组（54例）和miR-125b中/低表达亚组（48例）。miR-125b高表达亚组与miR-125b中/低表达亚组年龄、卵巢体积、骨龄、骨龄与年龄差、WSDS、HSDS、BMI SDS比较，差异无统计学意义（P>0.05）；miR-125b高表达亚组与miR-125b中/低表达亚组乳房发育年龄和乳腺Tanner分期比较，差异有统计学意义（P<0.05）。miR-125b高表达亚组雌二醇高于miR-125b中/低表达亚组（P<0.05）。经促性腺激素释放激素类似物（GnRHa）治疗后，miR-125b高表达亚组中维生素D正常者乳房发育消退比例高于维生素D缺乏者（P<0.05）；miR-125b高表达亚组中维生素D正常者与维生素D缺乏者生长速率恢复、骨龄减速比例比较，差异无统计学意义（P>0.05）。miR-125b中/低表达亚组中维生素D正常者与维生素D缺乏者乳房发育消退、生长速率恢复、骨龄减速比例比较，差异均无统计学意义（P>0.05）。结论　血清miR-125b在CPP女童中升高，与维生素D呈负相关，影响乳腺发育年龄，这可能与雌二醇的升高相关。血清miR-125b与维生素D联合检测可判定GnRHa治疗对CPP女童乳房发育消退的疗效。

Clinical Significance of Combined Detection of Serum miR-125b and Vitamin D in Female Children with Central Precocious Puberty

Background　Premature activation of hypothalamic-pituitary-gonadal axis is the main mechanism of central precocious puberty（CPP），but the mechanism of its activation is still unclear.mi-RNA may be involved in the development of precocious puberty.Objective　 To explore the relationships of serum microRNA-125b and vitamin D and hormone parameters，and analysis the clinical significance of combined detection of serum miR-125b and vitamin D.Methods　We enrolled 102 CPP female children（CPP group） and 102 age- and sex-matched physical examinees（control group） from Boai Hospital of Zhongshan Affiliated to Southern Medical University from July to September，from 2013 to 2016.The clinical parameters，such as age，height，weight，body mass index （BMI），breast development age，ovarian volume，bone age，bone age and age difference，WSDS，HSDS，and BMI SDS and distribution of Tanner stage were recorded.The expression level of miR-125b was detected by qRT-PCR.And the levels of 25-hydroxy-vitamin D（25-OH-D） and hormone parameters（free thyroxine，thyrotropin，estradiol，prolactin，luteinizing hormone and follicle-stimulating hormone）were detected using chemiluminiscence assay.Results　The expression level of serum miR-125b was higher in CPP group than that in the control group （P<0.05）．The serum miR-125b expression level was negatively correlated with 25-OH-D level in CPP group （r=-0.809 5，P<0.01）．CPP children with high miR-125b expression（high miR-125b expression subgroup，n=54） and those with low to medium miR-125b expression（low to medium miR-125b expression subgroup，n=48） showed significant differences in the mammogenesis age and distribution of Tanner stage（P<0.05），but not in the age，ovarian volume，bone age，bone age and age difference，WSDS，HSDS，and BMI SDS （P>0.05）．Moreover，high miR-125b expression subgroup had higher estradiol level than low to medium miR-125b expression subgroup（P<0.05）．After treated by gonadotropin-releasing hormone analogues（GnRHa），high miR-125b expression patients with normal vitamin D level had higher proportion of regression of breast development than those patients with decreased vitamin D level（P<0.05），but similar improvement in decreased growth velocity and early bone development（P>0.05）．Low to medium miR-125b expression patients with normal vitamin D level and those with decreased vitamin D level had no significant differences in the improvement in prepubertal mammogenesis，decreased growth velocity and early bone development（P>0.05）．Conclusion　The expression level of miR-125b was increased in CPP female children，which was negatively correlated with vitamin D level，and affected mammogenesis age.These may be related to the upregulation of estradiol.Combined detection of miR-125b and vitamin D could predicate the effect of GnRHa therapy on allometric growth of mammary parenchyma before puberty.