Акушерство и Гинекология Санкт-Петербурга. 2017; : 66-72
Клеточные механизмы формирования несостоятельности тазового дна
Аннотация
Несостоятельность тазового дна(НТД) — периферическое смещение матки и/или стенок влагалища в результате растяжения фасциальных структур малого таза. Согласно мировым данным от 2,9 до 53 % женщин отмечают те или иные проявления пролапса гениталий, причём до 47 %, по данным разных авторов, это женщины трудоспособного возраста. В настоящее время доказана связь «омоложения» НТД, легкие формы которой встречаются с частотой до 6,7% у женщин в периоде менопаузального перехода, а у женщин репродуктивного возраста — 22,2–25%. НТД крайне негативно отражается на качестве жизни пациенток и их трудоспособности.
Цель исследования: проанализировать патогенетические механизмы лежащих в основе НТД.
Материал и методы. Для формирования обзора предпринят анализ баз данных PubMed, EMBASE, MedLine, Cochrane и отобраны международные обзоры авторов, с наиболее крупными морфологическими и молекулярными исследованиями в той области.
Результаты. Ключевую роль в формировании НТД, помимо таких признанных факторов как беременность и роды, травма промежности, длительное повышение внутрибрюшного давления и возраст, имеют такие факторы как: биохимические особенности состава соединительной ткани, количество и качество в ней коллагена различных типов, эластина, и их соотношение, а так же действие на ее структуры различных биологически активных веществ, (MMP-2, TIMP-2 и TGF-β1) что, по мнению многих исследователей, регулируется генетически, а так же способность клеток соединительной ткани, в частности фибробластов, переносить окислительный стресс.
Заключение. При сравнении данных разных исследователей, зачастую контраверсионных, становится очевидным, что патогенез НТД требует проведения дальнейших исследований. Трансформирующий фактор роста (ТФР-1) стимулирует продукцию эластина и коллагена и ингибирует дегенерацию компонентов экстрацеллюлярного матрикса, и, он закономерно снижен у пациенток, страдающих НТД. По данным одних исследователей, количество эластина увеличивается в тканях у пациенток с НТД, другие же представляют контраверсионные результаты. На сегодня результатами экспериментальных работ доказано, что апоптоз клеток индуцируется механизмами окислительного стресса, а также влияет на метаболизм коллагена в фибробластах.
Список литературы
1. Руководство по амбулаторно-поликлинической помощи в акушерстве и гинекологии. Издательство «ГЭОТАР-Медиа»; 2016: 1023-1027.
2. Weber A.M., Brubaker L., Brown M.B. NICHD Pelvic Floor Disorders Network Investigators. Corrections to Report of a Trial of Burch Colposuspension. N Engl J Med. 2016; 374(23):2295. doi: 10.1056/NEJMc1605817.
3. DeLancey J.O., Swenson C.W., Morgan D.M., George J., Kearney R. Effect of Cystocele Repair on Cervix Location in Women With Uterus In Situ. Female Pelvic Med Reconstr Surg. 2017; 10:1097. doi: 10.1097/SPV.0000000000000438.
4. Lubowski D.Z., Patton V., Abraham E. Sacral nerve stimulation for faecal incontinence: medium-term follow-up from a single institution. ANZ J Surg. 2017; 87(6):462-466. doi: 10.1111/ans.13605.
5. Chung C.P., Cao S., Wakabayashi G., Han E.S. Management of pelvic floor disorder in a diethylstilbestrol daughter. Proc (Bayl Univ Med Cent). 2017; 30(3):291-292.
6. Meijerink A.M., van Rijssel R.H. Tissue composition of the vaginal wall in women with pelvic organ prolapse. Gynecol Obstet Invest. 2013; 75(1):21-27. doi: 10.1159/000341709.
7. Kim T., Sridharan I., Ma Y., Zhu B., Chi N., Kobak W. et al. Identifying distinct nanoscopic features of native collagen fibrils towards early diagnosis of pelvic organ prolapse. Nanomedicine. 2016; 12(3):667-675. doi: 10.1016/j.nano.2015.11.006.
8. Boreham M.K., Wai C.Y., Miller R.T., Schaffer J.I., Word R.A. Morphometric analysis of smooth muscle in the anterior vaginal wall of women with pelvic organ prolapse. Am J Obstet Gynecol 2002; 187(1):56–63.
9. Ruiz-Zapata A.M., Kerkhof M.H., Ghazanfari S., Zandieh-Doulabi B., Stoop R., Smit T.H., Helder M.N. Vaginal Fibroblastic Cells from Women with Pelvic Organ Prolapse Produce Matrices with Increased Stiffness and Collagen Content. Sci Rep. 2016; 6:22971. doi: 10.1038/srep22971.
10. Qi X.Y., Hong L., Guo F.Q., Fu Q., Chen L., Li B.S. Expression of transforming growth factorbeta 1 and connective tissue growth factor in women with pelvic organ prolapse. Saudi Med J 2011; 32(5):474–478.
11. Lin S.Y., Tee Y.T., Ng S.C., Chang H., Lin P., Chen G.D. Changes in the extracellular matrix in the anterior vagina of women with or without prolapse. Int Urogynecol J Pelvic Floor Dysfunct. 2007; 18(1):43–48. doi: 10.1007/s00192006-0090-1
12. Karam J.A., Vazquez D.V., Lin V.K., Zimmern P.E. Elastin expression and elastic fibre width in the anterior vaginal wall of postmenopausal women with and without prolapse. BJU Int. 2007;100(2):346–350. doi: 10.1111/j.1464410X.2007.06998.x.
13. Jackson S.R., Avery N.C., Tarlton J.F., Eckford S.D., Abrams P., Bailey A.J. Changes in metabolism of collagen in genitourinary prolapse. Lancet. 1996; 347(9016):1658–1661.
14. Connell K.A. Elastogenesis in the vaginal wall and pelvic-organ prolapse. N Engl J Med 2011; 364(24):2356–2358. doi: 10.1056/NEJMcibr1104976.
15. Kufaishi H., Alarab M., Drutz H., Lye S., Shynlova O. Static Mechanical Loading Influences the Expression of Extracellular Matrix and Cell Adhesion Proteins in Vaginal Cells Derived From Premenopausal Women With Severe Pelvic Organ Prolapse. Reprod Sci. 2016; 23(8):978-992. doi: 10.1177/1933719115625844.
16. Harman D. Aging: A theory based on free radical and radiation chemistry. J Gerontol. 1956; 11:298–300. doi: 10.1093/geronj/11.3.298
17. Liu C., Wang Y., Li B.S., Yang Q., Tang J.M., Min J., Hong S.S. Role of transforming growth factor β 1 in the pathogenesis of pelvic organ prolapse: A potential therapeutic target. Int J Mol Med. 2017; 40(2):347-356. doi: 10.3892/ijmm.2017.3042.
18. Pimentel D.R., Amin J.K., Xiao L., Miller T., Viereck J., Oliver-Krasinski J., et al. Reactive oxygen species mediate amplitude-dependent hypertrophic and apoptotic responses to mechanical stretch in cardiac myocytes. Circ Res. 2011; 89(5):453–460.
19. Kroese L.J., Scheffer P.G. 8-hydroxy-2′-deoxyguanosine and cardiovascular disease: A systematic review. Curr Atheroscler Rep. 2014; 16:452. doi: 10.1007/s11883-014-0452-y.
20. Gordon K.J., Blobe G.C. Role of transforming growth factor-beta superfamily signaling pathways in human disease. Biochim Biophys Acta. 2008;1782(4):197– 228. doi: 10.1016/j.bbadis.2008.01.006.
21. Moalli P.A., Klingensmith W.L., Meyn L.A., Zyczynski H.M. Regulation of matrix metalloproteinase expression by estrogen in fibroblasts that are derived from the pelvic floor. Am J Obstet Gynecol. 2002; 187(1):72–79
22. Swenson C.W., Simmen A.M., Berger M.B., Morgan D.M., DeLancey J.O. The long and short of it: anterior vaginal wall length before and after anterior repair. Int Urogynecol J. 2015; 26(7):1035-1039. doi: 10.1007/s00192-015-2636-6.
23. Berger M.B., Morgan D.M., DeLancey J.O. Levator ani defect scores and pelvic organ prolapse: is there a threshold effect? Int Urogynecol J. 2014; 25(10):13751379. doi: 10.1007/s00192-014-2388-8.
24. DeLancey J.O., Morgan D.M., Fenner D.E., Kearney R., Guire K., Miller J.M., et al. Comparison of levator ani muscle defects and function in women with and without pelvic organ prolapse. Obstet Gynecol. 2017; 109 (2 Pt 1):295–302. doi: 10.1097/01.AOG.0000250901.57095.ba
25. Swenson C.W., Kolenic G.E., Trowbridge E.R., Berger M.B., Lewicky-Gaupp C., Margulies R.U., et al. Obesity and stress urinary incontinence in women: compromised continence mechanism or excess bladder pressure during cough? Int Urogynecol J. 2017. doi: 10.1007/s00192-017-3279-6
Obstetrics and Gynaecology of Saint-Petersburg. 2017; : 66-72
Cellular mechanisms of insolvency of the pelvic floor
Abstract
Objective: Inconsistency of the pelvic floor peripheral displacement of the uterus and / or vagina walls as a result of stretching of the fascial structures of the pelvis. According to the world data, from 2.9 to 53% of women note certain manifestations of genital prolapse, and up to 47%, according to different authors, these are women of working age. At the present time, the connection between the “rejuvenation” of genital prolapse. The lung forms are found with a frequency of up to 6.7% in women in the premenopausal period, and in women of reproductive age 22.2-25%. POP has a very negative impact on the quality of life of patients and their ability to work.
Aim: analyze the pathogenetic mechanisms underlying the POP;
Materials and methods: To form the review, an analysis is made of the PubMed, EMBASE, MedLine, Cochrane databases and selected international reviews of authors, with the largest randomized controlled trials in that area.
Results. A key role in the formation of POP, in addition to such recognized factors as pregnancy and childbirth, perineal trauma, increased intraabdominal pressure and age, biochemical features of the composition of connective tissue, the amount of collagen of various types, elastin, and their ratio, as well as their effect on Its structure of various biologically active substances (MMP-2, TIMP-2 and TGF-β1), which, according to numerous researchers, is regulated genetically, as well as the ability of connective tissue cells, in particular fibroblasts, to undergo oxidative stress.
The conclusion. When comparing the data of different researchers, it becomes evident that the pathogenesis of POP requires further research. The transforming growth factor (TGF-1) stimulates the production of elastin and collagen and inhibits the degeneration of the components of the extracellular matrix, and it is naturally lowered in patients suffering from POP. According to some researchers, the amount of elastin increases in tissues in patients with POP, while others provide contraversial results. The results of experimental studies have shown that apoptosis of cells is induced by mechanisms of oxidative stress, and also affects the metabolism of collagen in fibroblasts.
References
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2. Weber A.M., Brubaker L., Brown M.B. NICHD Pelvic Floor Disorders Network Investigators. Corrections to Report of a Trial of Burch Colposuspension. N Engl J Med. 2016; 374(23):2295. doi: 10.1056/NEJMc1605817.
3. DeLancey J.O., Swenson C.W., Morgan D.M., George J., Kearney R. Effect of Cystocele Repair on Cervix Location in Women With Uterus In Situ. Female Pelvic Med Reconstr Surg. 2017; 10:1097. doi: 10.1097/SPV.0000000000000438.
4. Lubowski D.Z., Patton V., Abraham E. Sacral nerve stimulation for faecal incontinence: medium-term follow-up from a single institution. ANZ J Surg. 2017; 87(6):462-466. doi: 10.1111/ans.13605.
5. Chung C.P., Cao S., Wakabayashi G., Han E.S. Management of pelvic floor disorder in a diethylstilbestrol daughter. Proc (Bayl Univ Med Cent). 2017; 30(3):291-292.
6. Meijerink A.M., van Rijssel R.H. Tissue composition of the vaginal wall in women with pelvic organ prolapse. Gynecol Obstet Invest. 2013; 75(1):21-27. doi: 10.1159/000341709.
7. Kim T., Sridharan I., Ma Y., Zhu B., Chi N., Kobak W. et al. Identifying distinct nanoscopic features of native collagen fibrils towards early diagnosis of pelvic organ prolapse. Nanomedicine. 2016; 12(3):667-675. doi: 10.1016/j.nano.2015.11.006.
8. Boreham M.K., Wai C.Y., Miller R.T., Schaffer J.I., Word R.A. Morphometric analysis of smooth muscle in the anterior vaginal wall of women with pelvic organ prolapse. Am J Obstet Gynecol 2002; 187(1):56–63.
9. Ruiz-Zapata A.M., Kerkhof M.H., Ghazanfari S., Zandieh-Doulabi B., Stoop R., Smit T.H., Helder M.N. Vaginal Fibroblastic Cells from Women with Pelvic Organ Prolapse Produce Matrices with Increased Stiffness and Collagen Content. Sci Rep. 2016; 6:22971. doi: 10.1038/srep22971.
10. Qi X.Y., Hong L., Guo F.Q., Fu Q., Chen L., Li B.S. Expression of transforming growth factorbeta 1 and connective tissue growth factor in women with pelvic organ prolapse. Saudi Med J 2011; 32(5):474–478.
11. Lin S.Y., Tee Y.T., Ng S.C., Chang H., Lin P., Chen G.D. Changes in the extracellular matrix in the anterior vagina of women with or without prolapse. Int Urogynecol J Pelvic Floor Dysfunct. 2007; 18(1):43–48. doi: 10.1007/s00192006-0090-1
12. Karam J.A., Vazquez D.V., Lin V.K., Zimmern P.E. Elastin expression and elastic fibre width in the anterior vaginal wall of postmenopausal women with and without prolapse. BJU Int. 2007;100(2):346–350. doi: 10.1111/j.1464410X.2007.06998.x.
13. Jackson S.R., Avery N.C., Tarlton J.F., Eckford S.D., Abrams P., Bailey A.J. Changes in metabolism of collagen in genitourinary prolapse. Lancet. 1996; 347(9016):1658–1661.
14. Connell K.A. Elastogenesis in the vaginal wall and pelvic-organ prolapse. N Engl J Med 2011; 364(24):2356–2358. doi: 10.1056/NEJMcibr1104976.
15. Kufaishi H., Alarab M., Drutz H., Lye S., Shynlova O. Static Mechanical Loading Influences the Expression of Extracellular Matrix and Cell Adhesion Proteins in Vaginal Cells Derived From Premenopausal Women With Severe Pelvic Organ Prolapse. Reprod Sci. 2016; 23(8):978-992. doi: 10.1177/1933719115625844.
16. Harman D. Aging: A theory based on free radical and radiation chemistry. J Gerontol. 1956; 11:298–300. doi: 10.1093/geronj/11.3.298
17. Liu C., Wang Y., Li B.S., Yang Q., Tang J.M., Min J., Hong S.S. Role of transforming growth factor β 1 in the pathogenesis of pelvic organ prolapse: A potential therapeutic target. Int J Mol Med. 2017; 40(2):347-356. doi: 10.3892/ijmm.2017.3042.
18. Pimentel D.R., Amin J.K., Xiao L., Miller T., Viereck J., Oliver-Krasinski J., et al. Reactive oxygen species mediate amplitude-dependent hypertrophic and apoptotic responses to mechanical stretch in cardiac myocytes. Circ Res. 2011; 89(5):453–460.
19. Kroese L.J., Scheffer P.G. 8-hydroxy-2′-deoxyguanosine and cardiovascular disease: A systematic review. Curr Atheroscler Rep. 2014; 16:452. doi: 10.1007/s11883-014-0452-y.
20. Gordon K.J., Blobe G.C. Role of transforming growth factor-beta superfamily signaling pathways in human disease. Biochim Biophys Acta. 2008;1782(4):197– 228. doi: 10.1016/j.bbadis.2008.01.006.
21. Moalli P.A., Klingensmith W.L., Meyn L.A., Zyczynski H.M. Regulation of matrix metalloproteinase expression by estrogen in fibroblasts that are derived from the pelvic floor. Am J Obstet Gynecol. 2002; 187(1):72–79
22. Swenson C.W., Simmen A.M., Berger M.B., Morgan D.M., DeLancey J.O. The long and short of it: anterior vaginal wall length before and after anterior repair. Int Urogynecol J. 2015; 26(7):1035-1039. doi: 10.1007/s00192-015-2636-6.
23. Berger M.B., Morgan D.M., DeLancey J.O. Levator ani defect scores and pelvic organ prolapse: is there a threshold effect? Int Urogynecol J. 2014; 25(10):13751379. doi: 10.1007/s00192-014-2388-8.
24. DeLancey J.O., Morgan D.M., Fenner D.E., Kearney R., Guire K., Miller J.M., et al. Comparison of levator ani muscle defects and function in women with and without pelvic organ prolapse. Obstet Gynecol. 2017; 109 (2 Pt 1):295–302. doi: 10.1097/01.AOG.0000250901.57095.ba
25. Swenson C.W., Kolenic G.E., Trowbridge E.R., Berger M.B., Lewicky-Gaupp C., Margulies R.U., et al. Obesity and stress urinary incontinence in women: compromised continence mechanism or excess bladder pressure during cough? Int Urogynecol J. 2017. doi: 10.1007/s00192-017-3279-6
