维生素D缺乏与多囊卵巢综合征发病机制的相关性研究  

Correlation between vitamin D deficiency and the pathogenesis of polycystic ovary syndrome

作　　者：周加敏 吴婷婷 陈琳 陈燕[4] 许波群 ZHOU Jiamin;WU Tingting;CHEN Lin;CHEN Yan;XU Boqun(Department of Gynaecology and Obstetrics,Sir Run Run Hospital,Nanjing Medical University,Nanjing 211112;Department of Gynaecology and Obstetrics,Nanjing Red Cross Hospital,Nanjing 210001;Department of Gynaecology and Obstetrics,the Second Affiliated Hospital of Nanjing Medical University,Nanjing 210003;Department of Gynaecology and Obstetrics,the Fourth Affiliated Hospital of Nanjing Medical University,Nanjing 210031,China)

机构地区：[1]南京医科大学附属逸夫医院妇产科,江苏南京211112 [2]南京市红十字医院妇产科,江苏南京210001 [3]南京医科大学第二附属医院妇产科,江苏南京210003 [4]南京医科大学第四附属医院妇产科,江苏南京210031

出　　处：《南京医科大学学报（自然科学版）》2023年第7期934-944,共11页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81873820);南京市卫生科技发展专项资金项目(YKK19150)。

摘　　要：目的:探讨维生素D(vitamin D,VD)缺乏与多囊卵巢综合征(polycystic ovariansyndrome,PCOS)发病机制之间的关联。方法:检测34例PCOS患者和30例正常健康女性体内VD水平,并对其临床资料进行相关性分析;构建VD缺乏小鼠模型和PCOS小鼠模型,分为正常对照组(control,CTR组)、PCOS组、VD缺乏组(VD-组)、VD缺乏联合PCOS组(VD-+PCOS组)。观察各组小鼠动情周期及卵巢形态改变;检测小鼠血清性激素指标、糖脂代谢指标;实时定量聚合酶链反应(real⁃timequantitative polymerase chainreaction,RT⁃qPCR)法检测各组小鼠卵巢组织中激素合成酶及性激素受体mRNA表达水平。结果:PCOS女性体内25⁃羟维生素D[25⁃hydroxyvitaminD,25(OH)D]水平较正常健康女性明显降低[(16.49±6.50)ng/mL vs.(20.08±5.28)ng/mL,P=0.019]。PCOS组血清中黄体生成素(luteinizing hormone,LH)、睾酮(testosterone,TT)、黄体生成素与卵泡刺激素(follicular⁃stimulating hormone,FSH)比值即LH/FSH比值、游离雄激素指数(free androgenindex,FAI)水平均明显高于对照组,性激素结合蛋白(sex hormonebindingglobulin,SHBG)水平明显低于对照组,差异均有统计学意义(P<0.05)。相关性分析结果显示,总样本人群血清25(OH)D水平与LH(r=-0.271,P<0.05)、LH/FSH比值(r=-0.314,P<0.05)、TT(r=-0.276,P<0.05)、垂体泌乳素(prolactin,PRL)(r=-0.274,P<0.05)、FAI(r=-0.312,P<0.05)均呈负相关,PCOS患者血清25(OH)D水平与PRL存在负相关(r=-0.404,P<0.05)。VD缺乏使小鼠动情周期发生停滞;与CTR组相比,其余各组小鼠血清中LH水平明显升高(P<0.05);与CTR组相比,VD-组小鼠卵巢组织中雄激素受体(androgen receptor,AR)mRNA表达上调(P<0.05)。结论:PCOS患者存在VD缺乏现象,PCOS患者血清25(OH)D水平与PRL存在负相关关系。VD缺乏扰乱了小鼠正常动情周期并影响性激素水平,VD缺乏可能通过调节性激素受体表达来参与PCOS发生。Objective:To investigate the association between vitamin D(VD)deficiency and the pathogenesis of polycystic ovarian syndrome(PCOS).Methods:Vitamin D levels were detected in 34 patients with PCOS and 30 healthy women,and the correlation analysis was performed.Vitamin D deficiency mouse model and PCOS mouse model were constructed and divided into four groups:control group(CTR group),PCOS group,vitamin D deficiency group(VD-group),and vitamin D deficiency combined with PCOS group(VD-+PCOS group).Estrous cycle and ovary morphological changes were observed.Serum sex hormone indexes and glucose lipid metabolism indexes were detected.Real⁃time quantitative PCR(RT⁃qPCR)was used to detect the mRNA levels of hormone synthase and sex hormone receptor in ovarian tissues.Results:The levels of serum 25⁃hydroxyvitamin D[25(OH)D]in PCOS women were significantly lower than those in normal healthy women[(16.49±6.50)ng/mL vs.(20.08±5.28)ng/mL,P=0.019].The levels of luteinizing hormone(LH),testosterone(TT),LH/FSH ratio and free androgen index(FAI)in PCOS group were significantly higher than those in control group,while the levels of sex hormone binding globulin(SHBG)were significantly lower than those in control group,and the difference was statistically significant(P<0.05).Correlation analysis showed that serum 25(OH)D levels of the total sample population were negatively correlated with LH(r=-0.271,P<0.05),LH/FSH ratio(r=-0.314,P<0.05),TT(r=-0.276,P<0.05),prolactin(PRL)(r=-0.274,P<0.05)and FAI(r=-0.312,P<0.05)respectively,and serum 25(OH)D levels in PCOS patients were negatively correlated with PRL(r=-0.404,P<0.05).Vitamin D deficiency stalled the estrous cycle in mice.Compared with the CTR group,the serum LH levels of mice in other three groups were significantly increased(P<0.05).Compared with the CTR group,the mRNA level of androgen receptor(AR)in ovarian tissues of mice in VD-group was increased(P<0.05).Conclusion:Vitamin D deficiency existed in patients with PCOS.There was a negative correlation between serum 25(OH)D

关 键 词：多囊卵巢综合征 维生素D 泌乳素 动情周期 黄体生成素 雄激素受体 

分 类 号：R711.75[医药卫生—妇产科学]