雌激素诱导DCN基因甲基化在盆腔器官脱垂发病机制中的作用  

The role of estrogen-induced DCN gene methylation in the pathogenesis of pelvic organ prolapse

作　　者：崔淑岭 劳佩维[1] 沈柯炜 张英芝 CUI Shuling;LAO Peiwei;SHEN Kewei;ZHANG Yingzhi(Department of Gynaecology,the First Affiliated Hospital of Ningbo University,Ningbo,Zhejiang 315211,China)

机构地区：[1]宁波大学附属第一医院妇科,浙江宁波315211

出　　处：《中华全科医学》2024年第12期2049-2052,共4页Chinese Journal of General Practice

基　　金：浙江省医药卫生科技计划项目(2023KY1106)。

摘　　要：目的检测盆腔器官脱垂(POP)患者雌二醇(E2)、核心蛋白聚糖(DCN)基因甲基化水平,并研究其在POP发病机制中的作用。方法选取2023年1月—2024年1月于宁波大学附属第一医院妇科行盆底重建手术治疗的85例POP患者为研究对象,根据术前激素水平及绝经时间分为绝经后期组(PSM组,44例)和绝经过渡期组(TRM组,41例),另选取同期30例盆腔良性疾病患者为对照组。采用50 nmol/L雌激素(H-EST组)、2 nmol/L雌激素(L-EST组)、50 nmol/L雌激素联合ER拮抗(ESR siRNA,H-EST+siER组)及siER(siER组)处理原代成纤维细胞,未行任何处理的原代成纤维细胞为对照(CON组)。检测并比较E2、DCN、Ⅰ型胶原酶(COLⅠ)、E2受体(ER)、DCN基因甲基化差异。结果PSM组患者E2、DCN、COLⅠ及ER表达均显著低于TRM组和对照组(P<0.05),DCN甲基化率均显著高于TRM组和对照组(P<0.05)。PSM组和TRM组POP患者E2与DCN、COLⅠ均呈正相关关系(r_(s)=0.713、0.654、0.679、0.639,均P<0.05),与DCN基因甲基化呈负相关关系(r_(s)=-0.821、-0.806,P<0.05)。H-EST组、L-EST组细胞DCN、COLⅠ及ER表达均显著低于CON组、H-EST+siER组及siER组(P<0.05),DCN甲基化率均显著高于CON组、H-EST+siER组及siER组(P<0.05)。结论POP患者E2及DCN基因甲基化率显著升高,两者呈负相关关系,E2可能通过诱导DCN基因甲基化参与POP发病机制。Objective To detect the methylation of estradiol(E2)and decorin(DCN)genes in patients with pelvic organ prolapse(POP)and to study their role in the pathogenesis of POP.Methods A total of 85 POP patients who underwent surgery between January 2023 and January 2024 were selected for the postmenopause group(PSM group,n=44)and menopausal transition period group(TRM group,n=41),additionally,30 patients with pelvic benign diseases during the same period were selected as the control group.The Primary fibroblasts were treated with 50 nmol/L E2(H-EST group),2 nmol/L E2(L-EST group),and 50 nmol/L E2 in combination with an ER antagonist(ESR siRNA,H-EST+siER group).Detect and compare the methylation differences of the estradiol(E2),DCN,typeⅠcollagenase(COLⅠ),E2 receptor(ER)and DCN genes.Results The expressions of E2,DCN,COLⅠand ER in the PSM group were significantly lower than those in the TRM group and the control group(P<0.05),Furthermore the DCN methylation rate was significantly higher in the PSM group than in the TRM group and the control group(P<0.05).In patients with POP in the PSM group and TRM group,E2 was found to be positively correlated with the expression of DCN,COLⅠ,and ER(r_(s)=0.713,0.654,0.679,0.639,respectively,all P<0.05),and negatively correlated with DCN gene methylation(r_(s)=-0.821,-0.806,all P<0.05).The expressions of DCN,COLⅠand ER in cells of the H-EST group and L-EST group were significantly lower than those of the CON group,H-EST+siER group and siER group(P<0.05).Furthermore,the DCN methylation rate was significantly higher than that of the CON group,H-EST+siER group and siER group(P<0.05).Conclusion The methylation rate of DCN genes and E2 level is markedly elevated in patients with POP,and there is a negative correlation.E2 may play a role in the development of POP by inducing methylation of the DCN gene.

关 键 词：盆腔器官脱垂 雌激素 核心蛋白聚糖 甲基化 发病机制 

分 类 号：R711.2[医药卫生—妇产科学]