Vasin R V, Filimonov V B, Mnikhovich M V, Kaprin A D, Kostin A A, Vasina I V
Department of Urology and Nephrology of FGBOU VO Ryazan State Medical University of the Ministry of Health of Russia, Ryazan, Russia.
GBU City clinical hospital No 11, Ryazan, Russia.
Urologiia. 2019 Dec 31(6):12-20.
to study a correlation between clinical stage of pelvic organ prolapse (POP), a histological structure and results of immunohistochemical study of the vaginal wall were evaluated.
A total of 60 peri- and postmenopausal women (average age 61.9+/-8.4 years) with POP of stage II-IV, according to the POP-Q classification, or with stress urinary incontinence and cystocele of stage I-II, who undergone to surgical treatment, were included in the study. During a procedure, a biopsy from the anterior vaginal wall was taken. Depending on the stage of POP, patients was divided into two groups. In the group 1, 30 patients with stage I and II of POP were included, while group 2 included 30 women with POP of stage III and more. The control group (group 3) consisted of 20 patients without POP (mean age 63.4+/-11.0 years) who underwent a hysterectomy due to to other indications. A histological and immunohistochemical studies of vaginal wall tissue was performed in order to determine the tissue content of collagen type I and III; matrix metalloproteinases 1 and 2 (MMP-1 and MMP-2), a tissue inhibitor of metalloproteinases 1 (TIMP-1), vimentin and smooth muscle actin.
In contrast to two other groups, in group 2 there were significant changes in the connective tissue. Collagen has a form of fibrous mass with areas of reduced content. In addition, scarring areas with an increase in the content of type III collagen, a decrease in the amount of type I collagen and elastic fibers with significant fragmentation, were seen. Moreover, in patients with severe POP (III-IV), degradation of collagen fibers with a decrease in connective tissue strength and elasticity was detected. Women with POP had a low ratio of type I:III collagen. Analysis of the collagen content in the vaginal wall in patients with mild POP (I-II) revealed a significant increase in the level of collagen type I (p=0.0003) and a decrease in the content of type III (p=0.045), compared to patients with more severe POP (III-IV). The level of MMP-1 and MMP-2 in women with POP was higher, than in control group by 1.7 times (p<0.05). The content of TIMP-1 in the group 1 was significantly lower by 1.5 and 2.2 times, compared to group 2 and 3, respectively. An analysis of MMP-1 and MMP-2 concentration in patients of groups 1 and 2 revealed a significant (p=0.04) decrease in their activity in severe POP (III-IV). In women of the group 2, biopsy of the vaginal wall showed that expression of vimentin and smooth muscle actin in the connective tissue was significantly higher, than in group 1 and 3 (p<0.05). Vimentin expression in the group 2 was 1.4 and 2.6 times higher than in the group 1 and 3, respectively. In the control group, the expression of these markers in the vaginal wall was minimal and focal.
Our data indicate that fibrosis and degradation of the connective tissue in the vaginal wall predominate in POP, and these changes are a consequence, but not a cause of PG. The aggravation of degenerative changes in the connective tissue leads to the progression of POP.
研究盆腔器官脱垂（POP）的临床分期与阴道壁组织结构及免疫组化研究结果之间的相关性。
根据POP-Q分类，选取60例II-IV期盆腔器官脱垂的围绝经期和绝经后女性（平均年龄61.9±8.4岁），或I-II期压力性尿失禁合并膀胱膨出且接受手术治疗的患者纳入研究。手术过程中，从前阴道壁取活检组织。根据盆腔器官脱垂的分期，将患者分为两组。第1组纳入30例I期和II期盆腔器官脱垂患者，第2组纳入30例III期及以上盆腔器官脱垂的女性。对照组（第3组）由20例无盆腔器官脱垂的患者组成（平均年龄63.4±11.0岁），她们因其他指征接受了子宫切除术。对阴道壁组织进行组织学和免疫组化研究，以确定I型和III型胶原蛋白、基质金属蛋白酶1和2（MMP-1和MMP-2）、金属蛋白酶组织抑制剂1（TIMP-1）、波形蛋白和平滑肌肌动蛋白的组织含量。
与其他两组相比，第2组结缔组织有显著变化。胶原蛋白呈纤维状团块形式，含量减少区域明显。此外，可见瘢痕区域III型胶原蛋白含量增加，I型胶原蛋白和弹性纤维数量减少且明显碎片化。而且，在重度盆腔器官脱垂（III-IV期）患者中，检测到胶原纤维降解，结缔组织强度和弹性降低。盆腔器官脱垂患者I型与III型胶原蛋白比例较低。与重度盆腔器官脱垂（III-IV期）患者相比，轻度盆腔器官脱垂（I-II期）患者阴道壁胶原蛋白含量分析显示，I型胶原蛋白水平显著升高（p=0.0003），III型胶原蛋白含量降低（p=0.045）。盆腔器官脱垂女性MMP-1和MMP-2水平比对照组高1.7倍（p<0.05）。第1组TIMP-1含量分别比第2组和第3组显著低1.5倍和2.2倍。对第1组和第2组患者MMP-1和MMP-2浓度分析显示，重度盆腔器官脱垂（III-IV期）时其活性显著降低（p=0.04）。第2组女性阴道壁活检显示，结缔组织中波形蛋白和平滑肌肌动蛋白的表达显著高于第1组和第3组（p<0.05）。第2组波形蛋白表达分别比第1组和第3组高1.4倍和2.6倍。在对照组中，这些标志物在阴道壁的表达极少且呈局灶性。
我们的数据表明，阴道壁结缔组织的纤维化和降解在盆腔器官脱垂中占主导，这些变化是盆腔器官脱垂的结果而非原因。结缔组织退行性变的加重导致盆腔器官脱垂进展。
