Оксидативный стресс при синдроме поликистозных яичников: прогностическое значение, возможности коррекции

1 Ehrmann D. Polycystic ovary syndrome. New Eng J Med 2005; 352 (12): 1223–36.
2. Conway G, Dewailly D, Diamanti-Kandarakis E et al. The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur J Endocrinol 2014; 71 (4): 1–29.
3. Final Report National Institute of Health. Evidence-based Methodology Workshop on Polycystic Ovary Syndrome. December 3–5, 2012. Program Book. URL: https://prevention.nih.gov/docs/programs/pcos/FinalReport.pdf
4. The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19 (1): 41–7.
5. Биленко М.В. Ишемические и реперфузионные повреждения органов. М.: Медицина, 1989. / Bilenko M.V. Ischemic and reperfusion injury of organs. M.: Meditsina, 1989. [in Russian]
6. Цветикова Л.Н., Будневский А.В., Провоторов В.М., Филатова Ю.И. Особенности клинического течения бронхиальной астмы на фоне ингибирования оксидативного стресса. Лечащий врач. 2017; 2: 79. / Tsvetikova L.N., Budnevsky A.V., Provotorov V.M., Filatova Yu.I. Features of the clinical course of bronchial asthma on the background of inhibition of oxidative stress. Lechashchiy vrach. 2017; 2: 79. [in Russian]
7. Пасько В.Г., Ардашев В.Н., Титарова Ю.Ю., Тихонравов А.В. Оксидативный стресс при реперфузионном синдроме и методы его коррекции. Кремлевская медицина. Клин. вестн. 2017; 1: 150–3. / Pasko V.G., Ardashev V.N., Titarova Yu.Yu., Tikhonra-
vov A.V. The oxidative stress at the reperfusion syndrome and ways for its correction. Kremlevskaya meditsina. Klin. vestn. 2017; 1: 150–3. [in Russian]
8. Цой И.В. Оксидативный стресс и состояние сосудистого эндотелия при атеросклеротических стенозах внутренних сонных артерий. Мед. алфавит. 2017; 1 (4): 52–3. / Tsoy I.V. Oxidative stress and state of vascular endothelium in atherosclerotic internal carotid artery stenosis. Med. alfavit. 2017; 1 (4): 52–3. [in Russian]
9. Захаров И.С., Колпинский Г.И., Ушако-
ва Г.А., Вавин Г.В. Роль оксидативного стресса в формировании постменопаузального остеопороза. Гинекология. 2014; 16 (1): 41–3. / Zakharov I.S., Kolpinskiy G.I., Ushakova G.A., Wavin G.V. The role of oxidative stress in the formation of postmenopausal osteoporosis. Gynecology. 2014; 16 (1): 41–3. [in Russian]
10. Eleuterio NM, Palei AC, Machado JS et al. Role of adiponectin on antioxidant profile: evaluation during healthy and hypertensive disorders of pregnancy. Blood Press 2016; 2: 1–3.
11. Smriti K, Pai KM, Ravindranath V, Pentapati KC. Role of salivary malondialdehyde in assessment of oxidative stress among diabetics. J Oral Biol Craniofac Res 2016; 
6 (1): 41–4.
12. Babaee N, Hosseinkazemi H, Pouramir M et al. Salivary oxidant/antioxidant status and hematological parameters in patients with recurrent aphthous stomatitis. Caspian J Intern Med 2016; 7 (1): 13–8.
13. Murri M, Luque-Ramirez M, Insenser M. Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum Reprod Update 2013; 19 (3): 268–88.
14. Хащенко Е.П. Клинико-диагностические особенности синдрома поликистозных яичников у подростков с учетом провоспалительных факторов и оксидативного стресса. Дис. ... канд. мед. наук. М., 2017. / Khaschenko E.P. Clinical and diagnostic features of the syndrome of polycystic ovaries in adolescents, taking into account proinflammatory factors and oxidative stress: abstract of thesis … candidate of medical sciences. M., 2017. [in Russian]
15. Chen L, Xu WM, Zhang D. Association of abdominal obesity, insulin resistance, and oxidative stress in adipose tissue in women with polycystic ovary syndrome. Fertil Steril 2014; 102 (4): 1167–74.
16. Park K, Gross M, Lee D-H et al. Oxidative stress and insulin resistance. Diabetes Care 2009; 32 (7): 1302–7.
17. Enli Y, Fenkci SM, Fenkci V, Oztekin O. Serum Fetuin-A levels, insulin resistance and oxidative stress in women with polycystic ovary syndrome. Gynecol Endocrinol 2013; 29 (12): 1036–9.
18. Özer A, Bakacak M, Kıran H et al. Increased oxidative stress is associated with insulin resistance and infertility in polycystic ovary syndrome. Ginekologia Polska 2016; 87 (11): 733–8.
19. Onyango AN. The Contribution of Singlet Oxygen to Insulin Resistance. Oxid Med Cell Longev 2017: 8765972. DOI: 10.1155/2017/8765972. URL: http://doi.org/10.1155/2017/8765972
20. Fenkci V, Fenkci S, Yilmazer M, Serteser M. Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertil Steril 2003; 80 (1): 123–7.
21. Sabuncu T, Vural H, Harma M, Harma M. Oxidative stress in polycystic ovary syndrome and its contribution to the risk of cardiovascular disease. Clin Biochem 2001; 34 (5): 407–13.
22. Zuo T, Zhu M, Xu W. Roles of oxidative stress in polycystic ovary syndrome and cancers. Oxid Med Cell Longev 2016: 1–14.
23. Dumesic DA, Lobo RA. Cancer risk and PCOS. Steroids 2013; 78 (8): 782–5.
24. Schildkraut JM, Schwingl PJ, Bastos EA et al. Epithelial ovarian cancer risk among women with polycystic ovary syndrome. Obstet Gynecol 1996; 88 (4–1): 554–9.
25. Zhang R, Liu H, Bai H et al. Oxidative stress status in Chinese women with different clinical phenotypes of polycystic ovary syndrome. Clin Endocrinol (Oxf) 2017; 86 (1): 88–96.
26. Suresh S, Vijayakumar T. Correlations of insulin resistance and serum testosterone levels with LH: FSH ratio and oxidative stress in women with functional ovarian hyperandrogenism. Indian J Clin Biochem 2015; 30 (3): 345–50.
27. Prasad S, Tiwari M, Pandey AN et al. Impact of stress on oocyte quality and reproductive outcome. J Biomed Sci 2016; 23 (36): 1–12.
28. Rojas J, Chavez M, Olivar L. Polycystic ovary syndrome, insulin resistance, and obesity: navigating the patophysiologic labyrinth. Int J Reprod Med 2014: 1–17.
29. Agarwal A, Aponte-Mellado A, Premkumar BJ et al. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol 2012; 10: 49–135.
30. De Melo AS, Rodrigues JK, Jordao Junior AA. Oxidative stress and polycystic ovary syndrome: an evaluation during ovarian stimulation for intracytoplasmic sperm injection. Reproduction 2017; 153: 97–105.
31. Lean JM, Davies JT, Fuller K et al.  A crucial role for thiol antioxidants in estrogen-deficiency bone loss. J Clin Invest 2003; 112 (6): 915–23.
32. Kuscu NK, Var A. Oxidative stress but not endothelial dysfunction exists in non-obese, young group of patients with polycystic ovary syndrome. Acta Obstet Gynecol Scand 2009; 88 (5): 612–17.
33. Seleem AK, Refaeey AA, Shaalan D. Superoxide dismutase in polycystic ovary syndrome patients undergoing intracytoplasmic sperm injection. J Assist Reprod Genet 2014; 31 (4): 499–504.
34. Bausenwein J, Serke H, Eberle K. Elevated levels of oxidized low-density lipoprotein and of catalase activity in follicular fluid of obese women. Mol Hum Reprod 2010; 16 (2): 117–24.
35. Тутельян В.А., Княжев В.А., Хотимченко С.А. и др. Селен в организме человека: метаболизм, антиоксидантные свойства, роль в канцерогенезе. М.: Изд-во РАМН, 2002. / Tutelyan V.A., Knyazhev V.A., Khotimchenko S.A. et al. Selenium in the human body: metabolism, antioxidant properties, a role in carcinogenesis. M.: Izdatel'stvo RAMN, 2002.
[in Russian]
36. Каган В.Е., Савов В.М., Диденко В.В. и др. Соотношение активности антиоксидантных систем и эндогенного перекисного окисления липидов в миокарде левого и правого желудочков сердца. Бюл. эксперим. биологии. 1984; 6: 664–6. / Kagan V.E., Savov V.M., Didenko V.V. at al. The ratio of the activity of antioxidant systems and endogenous lipid peroxidation in the myocardium of the left and right ventricles of the heart. Byul. eksperim. biologii. 1984; 6: 664–6. [in Russian]
37. Данусевич И.Н. Нарушение овариальной функции у девушек с гипоталамическим синдромом (вопросы патогенеза и диагностики). Автореф. дис. … канд. мед. наук. Иркутск, 2000. / Danusevich I.N. Violation of ovarian function in women with hypothalamic syndrome (problems of pathogenesis and diagnosis). Abstract of thesis … candidate of med. sciences. Irkutsk, 2000. [in Russian]
38. Agarwal A, Gupta S, Sharma R. Oxidative stress and its implications in female infertility – a clinician’s perspective – review. Reprod Bio Medicine Online 2005; 11 (5): 641–50.
39. Hernández-Valencia M, Hernández-Quijano T, Vargas-Girón A et al. Decreased insulin resistance with amino acids, extracts and antioxidants in patients with polycystic ovary syndrome. Ginecol Obstet Mex 2013; 81 (10): 573–77.
40. Amini L, Tehranian N, Movahedin M. Antioxidants and management of polycystic ovary syndrome in Iran: A systematic review of clinical trials. Iran J Reprod Med 2015; 13 (1): 1–8.
41. Климова О.Ю., Бердникова Н.Г., Казаков Р.Е. Клинико-фармакологические аспекты применения витамина D: от известных фактов к поиску новых мишеней. Consilium Medicum. 2016; 18 (2): 109–16. / Klimova O.Yu., Berdnikova N.G., Kazakov R.E. Clinical and pharmacological aspects of the use of vitamin D: from the known facts to look for new targets. Consilium Medicum. 2016; 18 (2): 109–16. [in Russian]
42. Плещева А.В., Пигарова Е.А., Дзеранова Л.К. Витамин D и метаболизм: факты, мифы и предубеждения. Ожирение и метаболизм. 2012; 2: 33–42. / Plescheva A.V., Pigarova E.A., Dzeranova L.K. Vitamin D and metabolism: facts, myths and misconceptions. Ozhireniye i metabolizm. 2012; 2: 33–42. [in Russian]
43. Колпинский Г.И., Захаров И.С. Диагностика и прогнозирование постменопаузального остеопороза. Кемерово, 2015. / Kolpinskiy G.I., Zakharov I.S. Diagnostika i prognozirovanie postmenopauzal'nogo osteoporoza. Kemerovo, 2015. [in Russian]
44. Tao S, Yuan Q, Mao L et al. Vitamin D deficiency causes insulin resistance by provoking oxidative stress in hepatocytes. Oncotarget 2017; 40 (8): 67605–13.
45. Cui ZH, Yuan Q, Mao L. Insulin resistance in vitamin D-deficient mice is alleviated by n-acetylcysteine. Oncotarget 2017; 38 (8): 63281–9.
46. Rahsepar M, Mahjoub S, Esmaelzadeh S. Evaluation of vitamin D status and its correlation with oxidative stress markers in women with polycystic ovary syndrome. Int J Reprod Biomed 2017; 15 (6): 345–50.
47. Абсатарова Ю.С., Андреева Е.Н. Роль витамина D и мелатонина в патогенезе синдрома поликистозных яичников. Ожирение и метаболизм. 2014; 1: 20–3. / Absatarova Yu.S., Andreeva E.N. Rol' vitamina D i melatonina v patogeneze sindroma polikistoznykh iaichnikov. Ozhirenie i metabolizm. 2014; 1: 20–3. [in Russian]
48. Nikmard F, Hosseini E, Bakhtiyari M. Effects of melatonin on oocyte maturation in PCOS mouse model. Anim Sci J 2017; 88 (4): 586–92.
49. Захаров И.С., Колпинский Г.И., Ушакова Г.А., Вавин Г.В. Комплексный подход к диагностике и коррекции остеопоротических изменений у женщин в постменопаузе. Гинекология. 2015; 17 (3): 26–9. / Zakharov I.S., Kolpinskiy G.I., Ushakova G.A, Wavin G.V. An integrated approach to the diagnosis and correction of osteoporotic changes in postmenopausal women. Gynecology. 2015; 17 (3): 26–9. [in Russian]
50. Борисов В.В. Причины расстройств и перспективы улучшения репродуктивного здоровья населения России. Клиническая лекция. Consilium Medicum. 2017; 19 (7): 70–5. / Borisov V.V. Causes of disorders and prospects for improving reproductive health in Russia. Clinical lecture. Consilium Medicum. 2017; 19 (7): 70–5. [in Russian]

________________________________________________

1 Ehrmann D. Polycystic ovary syndrome. New Eng J Med 2005; 352 (12): 1223–36.
2. Conway G, Dewailly D, Diamanti-Kandarakis E et al. The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur J Endocrinol 2014; 71 (4): 1–29.
3. Final Report National Institute of Health. Evidence-based Methodology Workshop on Polycystic Ovary Syndrome. December 3–5, 2012. Program Book. URL: https://prevention.nih.gov/docs/programs/pcos/FinalReport.pdf
4. The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19 (1): 41–7.
5.  Bilenko M.V. Ischemic and reperfusion injury of organs. M.: Meditsina, 1989. [in Russian]
6. Tsvetikova L.N., Budnevsky A.V., Provotorov V.M., Filatova Yu.I. Features of the clinical course of bronchial asthma on the background of inhibition of oxidative stress. Lechashchiy vrach. 2017; 2: 79. [in Russian]
7.  Pasko V.G., Ardashev V.N., Titarova Yu.Yu., Tikhonra-
vov A.V. The oxidative stress at the reperfusion syndrome and ways for its correction. Kremlevskaya meditsina. Klin. vestn. 2017; 1: 150–3. [in Russian]
8.  Tsoy I.V. Oxidative stress and state of vascular endothelium in atherosclerotic internal carotid artery stenosis. Med. alfavit. 2017; 1 (4): 52–3. [in Russian]
9.  Zakharov I.S., Kolpinskiy G.I., Ushakova G.A., Wavin G.V. The role of oxidative stress in the formation of postmenopausal osteoporosis. Gynecology. 2014; 16 (1): 41–3. [in Russian]
10. Eleuterio NM, Palei AC, Machado JS et al. Role of adiponectin on antioxidant profile: evaluation during healthy and hypertensive disorders of pregnancy. Blood Press 2016; 2: 1–3.
11. Smriti K, Pai KM, Ravindranath V, Pentapati KC. Role of salivary malondialdehyde in assessment of oxidative stress among diabetics. J Oral Biol Craniofac Res 2016; 
6 (1): 41–4.
12. Babaee N, Hosseinkazemi H, Pouramir M et al. Salivary oxidant/antioxidant status and hematological parameters in patients with recurrent aphthous stomatitis. Caspian J Intern Med 2016; 7 (1): 13–8.
13. Murri M, Luque-Ramirez M, Insenser M. Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum Reprod Update 2013; 19 (3): 268–88.
14.  Khaschenko E.P. Clinical and diagnostic features of the syndrome of polycystic ovaries in adolescents, taking into account proinflammatory factors and oxidative stress: abstract of thesis … candidate of medical sciences. M., 2017. [in Russian]
15. Chen L, Xu WM, Zhang D. Association of abdominal obesity, insulin resistance, and oxidative stress in adipose tissue in women with polycystic ovary syndrome. Fertil Steril 2014; 102 (4): 1167–74.
16. Park K, Gross M, Lee D-H et al. Oxidative stress and insulin resistance. Diabetes Care 2009; 32 (7): 1302–7.
17. Enli Y, Fenkci SM, Fenkci V, Oztekin O. Serum Fetuin-A levels, insulin resistance and oxidative stress in women with polycystic ovary syndrome. Gynecol Endocrinol 2013; 29 (12): 1036–9.
18. Özer A, Bakacak M, Kıran H et al. Increased oxidative stress is associated with insulin resistance and infertility in polycystic ovary syndrome. Ginekologia Polska 2016; 87 (11): 733–8.
19. Onyango AN. The Contribution of Singlet Oxygen to Insulin Resistance. Oxid Med Cell Longev 2017: 8765972. DOI: 10.1155/2017/8765972. URL: http://doi.org/10.1155/2017/8765972
20. Fenkci V, Fenkci S, Yilmazer M, Serteser M. Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertil Steril 2003; 80 (1): 123–7.
21. Sabuncu T, Vural H, Harma M, Harma M. Oxidative stress in polycystic ovary syndrome and its contribution to the risk of cardiovascular disease. Clin Biochem 2001; 34 (5): 407–13.
22. Zuo T, Zhu M, Xu W. Roles of oxidative stress in polycystic ovary syndrome and cancers. Oxid Med Cell Longev 2016: 1–14.
23. Dumesic DA, Lobo RA. Cancer risk and PCOS. Steroids 2013; 78 (8): 782–5.
24. Schildkraut JM, Schwingl PJ, Bastos EA et al. Epithelial ovarian cancer risk among women with polycystic ovary syndrome. Obstet Gynecol 1996; 88 (4–1): 554–9.
25. Zhang R, Liu H, Bai H et al. Oxidative stress status in Chinese women with different clinical phenotypes of polycystic ovary syndrome. Clin Endocrinol (Oxf) 2017; 86 (1): 88–96.
26. Suresh S, Vijayakumar T. Correlations of insulin resistance and serum testosterone levels with LH: FSH ratio and oxidative stress in women with functional ovarian hyperandrogenism. Indian J Clin Biochem 2015; 30 (3): 345–50.
27. Prasad S, Tiwari M, Pandey AN et al. Impact of stress on oocyte quality and reproductive outcome. J Biomed Sci 2016; 23 (36): 1–12.
28. Rojas J, Chavez M, Olivar L. Polycystic ovary syndrome, insulin resistance, and obesity: navigating the patophysiologic labyrinth. Int J Reprod Med 2014: 1–17.
29. Agarwal A, Aponte-Mellado A, Premkumar BJ et al. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol 2012; 10: 49–135.
30. De Melo AS, Rodrigues JK, Jordao Junior AA. Oxidative stress and polycystic ovary syndrome: an evaluation during ovarian stimulation for intracytoplasmic sperm injection. Reproduction 2017; 153: 97–105.
31. Lean JM, Davies JT, Fuller K et al.  A crucial role for thiol antioxidants in estrogen-deficiency bone loss. J Clin Invest 2003; 112 (6): 915–23.
32. Kuscu NK, Var A. Oxidative stress but not endothelial dysfunction exists in non-obese, young group of patients with polycystic ovary syndrome. Acta Obstet Gynecol Scand 2009; 88 (5): 612–17.
33. Seleem AK, Refaeey AA, Shaalan D. Superoxide dismutase in polycystic ovary syndrome patients undergoing intracytoplasmic sperm injection. J Assist Reprod Genet 2014; 31 (4): 499–504.
34. Bausenwein J, Serke H, Eberle K. Elevated levels of oxidized low-density lipoprotein and of catalase activity in follicular fluid of obese women. Mol Hum Reprod 2010; 16 (2): 117–24.
35. Tutelyan V.A., Knyazhev V.A., Khotimchenko S.A. et al. Selenium in the human body: metabolism, antioxidant properties, a role in carcinogenesis. M.: Izdatel'stvo RAMN, 2002.
[in Russian]
36. Kagan V.E., Savov V.M., Didenko V.V. at al. The ratio of the activity of antioxidant systems and endogenous lipid peroxidation in the myocardium of the left and right ventricles of the heart. Byul. eksperim. biologii. 1984; 6: 664–6. [in Russian]
37. Danusevich I.N. Violation of ovarian function in women with hypothalamic syndrome (problems of pathogenesis and diagnosis). Abstract of thesis … candidate of med. sciences. Irkutsk, 2000. [in Russian]
38. Agarwal A, Gupta S, Sharma R. Oxidative stress and its implications in female infertility – a clinician’s perspective – review. Reprod Bio Medicine Online 2005; 11 (5): 641–50.
39. Hernández-Valencia M, Hernández-Quijano T, Vargas-Girón A et al. Decreased insulin resistance with amino acids, extracts and antioxidants in patients with polycystic ovary syndrome. Ginecol Obstet Mex 2013; 81 (10): 573–77.
40. Amini L, Tehranian N, Movahedin M. Antioxidants and management of polycystic ovary syndrome in Iran: A systematic review of clinical trials. Iran J Reprod Med 2015; 13 (1): 1–8.
41. Klimova O.Yu., Berdnikova N.G., Kazakov R.E. Clinical and pharmacological aspects of the use of vitamin D: from the known facts to look for new targets. Consilium Medicum. 2016; 18 (2): 109–16. [in Russian]
42. Plescheva A.V., Pigarova E.A., Dzeranova L.K. Vitamin D and metabolism: facts, myths and misconceptions. Ozhireniye i metabolizm. 2012; 2: 33–42. [in Russian]
43. Kolpinskiy G.I., Zakharov I.S. Diagnostika i prognozirovanie postmenopauzal'nogo osteoporoza. Kemerovo, 2015. [in Russian]
44. Tao S, Yuan Q, Mao L et al. Vitamin D deficiency causes insulin resistance by provoking oxidative stress in hepatocytes. Oncotarget 2017; 40 (8): 67605–13.
45. Cui ZH, Yuan Q, Mao L. Insulin resistance in vitamin D-deficient mice is alleviated by n-acetylcysteine. Oncotarget 2017; 38 (8): 63281–9.
46. Rahsepar M, Mahjoub S, Esmaelzadeh S. Evaluation of vitamin D status and its correlation with oxidative stress markers in women with polycystic ovary syndrome. Int J Reprod Biomed 2017; 15 (6): 345–50.
47. Absatarova Yu.S., Andreeva E.N. Rol' vitamina D i melatonina v patogeneze sindroma polikistoznykh iaichnikov. Ozhirenie i metabolizm. 2014; 1: 20–3. [in Russian]
48. Nikmard F, Hosseini E, Bakhtiyari M. Effects of melatonin on oocyte maturation in PCOS mouse model. Anim Sci J 2017; 88 (4): 586–92.
49.  Zakharov I.S., Kolpinskiy G.I., Ushakova G.A, Wavin G.V. An integrated approach to the diagnosis and correction of osteoporotic changes in postmenopausal women. Gynecology. 2015; 17 (3): 26–9. [in Russian]
50. Borisov V.V. Causes of disorders and prospects for improving reproductive health in Russia. Clinical lecture. Consilium Medicum. 2017; 19 (7): 70–5. [in Russian]

И.С.Захаров*1, Е.Л.Букреева2

1. ФГБОУ ВО «Кемеровский государственный медицинский университет» Минздрава России. 650056, Россия, Кемерово, ул. Ворошилова, д. 22А;
2. ГАУЗ КО «Кемеровская городская клиническая больница №1 им. М.Н.Горбуновой». 650025, Россия, Кемерово, ул. Дарвина, д. 2
*isza@mail.ru

________________________________________________

I.S.Zakharov*1, E.L.Bukreeva2

1. Kemerovo State Medical University of the Ministry of Health of the Russian Federation. 650029, Russian Federation, Kemerovo, ul. Voroshilova, d. 22a;
2. M.N.Gorbunova Kemerovo City Clinical Hospital №1. 650025, Russian Federation, Kemerovo, ul. Darvina, d. 2
*isza@mail.ru