Zong Wenjun, Jallah Zegbeh C, Stein Suzan E, Abramowitch Steven D, Moalli Pamela A
Department of Obstetrics & Gynecology and Reproductive Sciences, Division of Urogynecology & Reconstructive Pelvic Surgery and Magee-Womens Research Institute.
Female Pelvic Med Reconstr Surg. 2010 Sep 1;16(5):257-262. doi: 10.1097/SPV.0b013e3181ed30d2.
The objectives were 1) to determine whether human vaginal fibroblasts are mechanosensitive and 2) to study the impact of mechanical stretch on these cells in the presence and absence of hormones. METHODS: Fibroblasts obtained from biopsies of full thickness vagina of 3 women were cyclically biaxially stretched at a magnitude of 8 and 16% for 72 hours with or without 17-β-estradiol plus progesterone. Culture media was collected and total collagenase activity was measured in duplicate using a fluorogenic substrate degradation assay. Data were analyzed at the 0.05 level of significance using Student t-test. RESULTS: Cells remained 90% viable throughout the experiments. Relative to the controls, hormonal treatment alone decreased collagenase activity (P=0.008). In the presence of mechanical stretch and in the absence of hormones, collagenase activity was increased (8% elongation, P=0.04; 16% elongation, P=0.001, respectively). The increase in collagenase activity was linearly correlated with magnitude (P<0.001). In the presence of hormones, the increase in enzyme activity by mechanical stretch was suppressed to baseline control levels (P=0.46). There was no difference in suppression by hormones by magnitude (P=0.48). CONCLUSIONS: Vaginal connective tissue fibroblasts are mechanosensitive with increased collagenase activity in the presence of stretch. This degradative behavior is inhibited in the presence of hormones. The data provide a mechanism by which events that induce vaginal stretch may lead to progression of pelvic organ prolapse, particularly, in the absence of hormones. Further studies are needed to determine whether these events lead to tissue with inferior mechanical properties.
本研究旨在1)确定人类阴道成纤维细胞是否具有机械敏感性,以及2)研究在有或无激素存在的情况下,机械拉伸对这些细胞的影响。方法:从3名女性全层阴道活检组织中获取的成纤维细胞,在有或无17-β-雌二醇加孕酮的情况下,以8%和16%的幅度进行双轴循环拉伸72小时。收集培养基,并使用荧光底物降解测定法一式两份测量总胶原酶活性。使用学生t检验在0.05的显著性水平上分析数据。结果:在整个实验过程中,细胞存活率保持在90%。相对于对照组,单独的激素处理降低了胶原酶活性(P=0.008)。在存在机械拉伸且无激素的情况下,胶原酶活性增加(伸长8%时,P=0.04;伸长16%时,P=0.001)。胶原酶活性的增加与拉伸幅度呈线性相关(P<0.001)。在有激素存在的情况下,机械拉伸引起的酶活性增加被抑制至基线对照水平(P=0.46)。激素对不同幅度拉伸的抑制作用无差异(P=0.48)。结论:阴道结缔组织成纤维细胞具有机械敏感性,拉伸时胶原酶活性增加。这种降解行为在有激素存在时受到抑制。这些数据提供了一种机制,通过该机制,诱导阴道拉伸的事件可能导致盆腔器官脱垂的进展,特别是在无激素的情况下。需要进一步研究以确定这些事件是否会导致机械性能较差的组织。