Gustilo-Ashby Arlan Marcus, Lee Una, Vurbic Drina, Sypert David, Kuang Mei, Daneshgari Firouz, Barber Matthew D, Damaser Margot S
From the *Center for Urogynecology and Reconstructive Surgery, Obstetrics, Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH; †Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH; ‡Research Service, Department of Veterans Affairs Medical Center, Louis Stokes Cleveland, Cleveland, OH; and §Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH.
Female Pelvic Med Reconstr Surg. 2010 Jan;16(1):21-30. doi: 10.1097/SPV.0b013e3181d00035.
: Lysyl oxidase like-1 (LOXL1) knockout mice have abnormal elastic fiber homeostasis and frequently develop pelvic floor dysfunction after pregnancy and delivery. The objective of this study was to test the hypothesis that tissue changes associated with vaginal delivery lead to pelvic floor dysfunction as a result of abnormal elastic fiber homeostasis.
: Female LOXL1 knockout mice delivered either spontaneously or by cesarean delivery. Mice were assessed weekly for pelvic organ prolapse (POP). At 12 weeks postpartum, lower urinary tract function was assessed by cystometry and leak-point pressure testing. Urethrovaginal cross-sections were analyzed using a histologic grading scale to assess elastin fiber disorganization.
: A total of 39 mice delivered by spontaneous vaginal delivery and 36 by cesarean delivery. Twelve weeks after spontaneous vaginal delivery or cesarean delivery, 23 (59%) and 11 (31%) mice had developed POP, respectively. The mean time to develop POP was 7.2 weeks after spontaneous vaginal delivery and 10.5 weeks after cesarean delivery (log rank, P = 0.0008). The Cox proportional hazard ratio was 0.55 (95% confidence interval, 0.38-0.79). Mice with POP had increased frequency of bladder contractions not associated with voiding during cystometry (P = 0.02). POP, but not mode of delivery, was associated with increased elastic fiber disorganization.
: Cesarean delivery delays the development of POP in LOXL1 knockout mice. POP is associated with increased bladder contraction frequency and increased elastic fiber disorganization in the urethra and vagina. The mechanisms underlying these findings warrant further investigation.
赖氨酰氧化酶样1（LOXL1）基因敲除小鼠存在弹性纤维稳态异常，且在妊娠和分娩后常发生盆底功能障碍。本研究的目的是检验以下假设：与阴道分娩相关的组织变化由于弹性纤维稳态异常而导致盆底功能障碍。
雌性LOXL1基因敲除小鼠通过自然分娩或剖宫产分娩。每周对小鼠进行盆底器官脱垂（POP）评估。产后12周，通过膀胱测压和漏点压力测试评估下尿路功能。使用组织学分级量表分析尿道阴道横断面，以评估弹性纤维紊乱情况。
共有39只小鼠通过自然阴道分娩，36只通过剖宫产分娩。自然阴道分娩或剖宫产后12周，分别有23只（59%）和11只（31%）小鼠发生了POP。自然阴道分娩后发生POP的平均时间为7.2周，剖宫产后为10.5周（对数秩检验，P = 0.0008）。Cox比例风险比为0.55（95%置信区间，0.38 - 0.79）。发生POP的小鼠在膀胱测压期间与排尿无关的膀胱收缩频率增加（P = 0.02）。POP与弹性纤维紊乱增加有关，而与分娩方式无关。
剖宫产可延迟LOXL1基因敲除小鼠POP的发生。POP与膀胱收缩频率增加以及尿道和阴道弹性纤维紊乱增加有关。这些发现的潜在机制值得进一步研究。
