盆腔器官脱垂患者盆底结缔组织中Fibulin-5和LOXL1的表达及意义

摘要

目的:探讨盆底结缔组织中弹性纤维相关基因Fibulin-5和类赖氨酰氧化酶1(LOXL1)的表达与盆腔器官脱垂(POP)发生的关系.方法:用Real-time RT-PCR检测24例POP患者(POP组)和22例因妇科良性疾病行子宫全切术患者(对照组)的骶韧带和(或)阴道前壁组织Fibulin-5及LOXL1的mRNA表达水平；同时采用免疫组化ElivisionTM Plus两步法检测其蛋白的表达.结果:①POP组患者骶韧带和阴道前壁组织中Fibulin-5 mRNA的表达明显低于对照组,而LOXL1 mRNA的表达明显高于对照组(P＜0.05)；且POPⅡ、Ⅲ期患者骶韧带组织中Fibulin-5 mRNA的表达量均数随POP程度加重而降低,LOXL1 mRNA的表达量均数随POP程度加重而增加(P＜0.05).②Fibulin-5蛋白的表达主要定位于细胞外基质,LOXL1蛋白的表达主要定位于成纤维细胞和平滑肌细胞胞质中.POP组骶韧带及阴道前壁组织中Fibulin-5蛋白的阳性表达率低于对照组(P＜0.05),而LOXL1蛋白的阳性表达率高于对照组(P＜0.05).结论:POP患者盆底结缔组织中Fibulin-5 mRNA和蛋白的表达降低,LOXL1 mRNA和蛋白的表达升高,且变化的程度均与脱垂程度有关.两者可能通过影响弹性纤维的聚合过程,促进POP的发病.%Objective:To investigate the expressions of Fibulin-5 and lysyl oxidase-like 1 (LOXL1) in uterosacral ligaments and anterior vaginal wall in women with pelvic organ prolapse (POP) and their relationship with the occurrence of POP.Methods:Quantitative real-time polymerase chain reaction (real-time RT-PCR) was performed to measure the level of Fibulin-5 and LOXL1 mRNA in the uterosacral ligaments and anterior vaginal wall of 24 POP patients(POP group) and 22 patients who received hysterectomy for benign gynecological diseases (control group).Simultaneously,Fibulin-5 and LOXL1 protein expressions were assessed by immunohistochemistry.Results:①Comparing to controls,significant decrease in Fibulin-5 mRNA expression and increase of LOXL1 mRNA expression were found in the uterosacral ligaments and anterior vaginal wall of patients with POP (P＜0.05).In patients with POP Ⅱ,Ⅲ stage,the level of Fibulin-5 in the uterosacral ligaments was decreased with increasing degrees of prolapse,while the level of LOXL1 was increased with increasing degrees of prolapse (P ＜ 0.05).②2-Fibulin-5 was almost expressed in the extracellular matrix and LOXL1 in the cytoplasm of fibroblasts and smooth muscle cells.Comparing with controls,the positive rate of Fibulin-5 expression in the uterosacral ligaments and anterior vaginal wall was significantly lower in patients with POP while the positive rate of LOXL1 was significantly higher (P＜0.05).Conclusions:There is a decreased expression of Fibulin-5 and an increased expression of LOXL1 in the uterosacral ligaments and anterior vaginal wall of patients with POP.Alterations of Fibulin-5 and LOXL1 expression might impact the synthesis of elastic fibers and hence induce POP.