medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»medalphabet-654Research ArticleСтатьиРоль нарушений антиоксидантной защиты в течении внутрипеченочного холестаза беременных и развитии гестационных осложненийRole of antioxidant defense disorders during intrahepatic cholestasis of pregnant women and development of gestational complicationsУспенскаяЮ. Б.UspenskayaYu. B.noemail@neicon.ruШептулинА. А.SheptulinA. A.noemail@neicon.ruКузнецоваИ. В.KuznetsovaI. V.noemail@neicon.ruГончаренкоН. В.GoncharenkoN. V.noemail@neicon.ruГерасимовА. Н.GerasimovA. N.noemail@neicon.ruФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Минздрава России (Сеченовский университет)РоссияFirst Moscow State Medical University n.a. I. M. SechenovRussian Federation201828042018213Современная гинекология2630Copyright © Успенская Ю.Б., Шептулин А.А., Кузнецова И.В., Гончаренко Н.В., Герасимов А.Н., 20182018Успенская Ю.Б., Шептулин А.А., Кузнецова И.В., Гончаренко Н.В., Герасимов А.Н.Uspenskaya Y.B., Sheptulin A.A., Kuznetsova I.V., Goncharenko N.V., Gerasimov A.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/654

До настоящего времени не до конца ясны механизмы возникновения гестационных осложнений при внутрипеченочном холестазе беременных (ВХБ) и не известны четкие предикторы их развития. Окислительный стресс и нарушения антиоксидантой защиты, являющиеся патогенетическим звеном различной патологии беременности, могут играть роль в развитии осложнений беременности при ВХБ и служить прогностическим маркером их возникновения. Цель исследования. Определение роли нарушений антиоксидантного статуса в развитии осложнений беременности у пациенток с ВХБ. Материалы исследования. В проспективное исследование были включены 97 беременных женщин, имевших ВХБ. Из них методом случайной выборки была выделена группа 57 пациенток. Пациенткам выделенной группы проводилось клиническое и лабораторное обследование с определением биохимических маркеров повреждения функции печени, УЗИ. Антиоксидантный статус оценивался на основании определения содержания ферментов антиоксидантной защиты (супероксиддисмутаза [СОД], глутатионпероксидаза [ГТП]) и их коферментов (цинк, селен). Выраженность кожного зуда устанавливалась в диапазоне от 0 до 3 исходно (при выявлении ВХБ), а также через 1 и 2 недели лечения. Лечение проводилось препаратами урсодеоксихолевой кислоты в дозе от 500 мг до 2 г в сутки. Результаты. У пациенток с ВХБ, имевших осложнения беременности (преждевременные роды, внутриутробная гипоксия плода, преэклампсия, необходимость в проведении кесарева сечения), отмечены более низкие уровни СОД, ГТП, селена и цинка в сравнении с пациентками, не имевшими этих осложнений. Факторами, способствующими нарушениям антиоксидантной защиты у пациенток с ВХБ, оказались его раннее начало и длительное течение, многоплодная беременность, применение программ вспомогательных репродуктивных технологий и препаратов половых гормонов, наличие билиарного сладжа и низкая эффективность лечения кожного зуда. Заключение. Истощение защитных механизмов, препятствующих развитию окислительного стресса, является одним из звеньев патогенеза развития осложнений беременности у пациенток с ВХБ. Нарушения антиоксидантной защиты при ВХБ можно рассматривать как предиктор развития осложнений беременности и показание для активного ведения пациенток.

To date, the mechanisms of the onset of gestational complications in intrahepatic cholestasis of pregnant women (VCB) are not fully understood, and clear predictors of their development are not known. Oxidative stress and antioxidant defense disorders, which are a pathogenetic link in various pathologies of pregnancy, can play a role in the development of complications of pregnancy in VCB and serve as a prognostic marker for their occurrence. Purpose of the study. Determination of the role of antioxidant status disorders in the development of complications of pregnancy in patients with VCB. Materials of the study. A prospective study included 97 pregnant women who had VCB. Of these, a group of 57 patients was randomly selected. Patients of the isolated group underwent clinical and laboratory examination with determination of biochemical markers of damage to liver function, ultrasound. Antioxidant status was assessed on the basis of the determination of the content of antioxidant defense enzymes (superoxide dismutase [SOD], glutathione peroxidase [GTP]) and their coenzymes (zinc, selenium). Severe pruritus was established in the range from 0 to 3 initially (with the detection of VCB), and after 1 and 2 weeks of treatment. The treatment was carried out with ursodeoxycholic acid preparations at a dose of 500 mg to 2 g per day. Results. in patients with VCB who had complications of pregnancy (preterm delivery, intrauterine fetal hypoxia, preeclampsia, the need for caesarean section), lower levels of SOD, GTP, selenium and zinc were observed compared to patients who did not have these complications. Factors contributing to the disturbance of antioxidant protection in patients with VCB were its early onset and prolonged course, multiple pregnancies, the use of assisted reproductive technologies and sex hormone drugs, the presence of biliary sludge and the low efficacy of treatment of pruritus. The conclusion. The depletion of protective mechanisms that inhibit the development of oxidative stress is one of the links in the pathogenesis of complications of pregnancy in patients with VCB. Disorders of antioxidant protection in VCB can be considered as a predictor of the development of pregnancy complications and an indication for active management of patients.

внутрипеченочный холестаз беременныхокислительный стрессферменты антиоксидантной защитыглутатионпероксидазасупероксиддисмутазаселенгестационные осложненияintrahepatic cholestasis of pregnancyoxidative stressenzymes of antioxidant defenseglutathione peroxidasesuperoxide dismutaseseleniumgestational complicationsReferencesFloreani A, Carderi I, Paternoster D, Soardo G, Azzaroli F, Esposito W, et al. Intrahepatic cholestasis of pregnancy: three novel MDR3 gene mutations. Aliment Pharmacol Ther. Jun 2006; 23 (11): 1649-53.Floreani A, Carderi I, Paternoster D, Soardo G, Azzaroli F, Esposito W, et al. Intrahepatic cholestasis of pregnancy: three novel MDR3 gene mutations. Aliment Pharmacol Ther. Jun 2006; 23 (11): 1649-53.Williamson C, Geenes V. Intrahepatic cholestasis of pregnancy. Obstet Gynecol. 20J4 Jul; 124 (1): J20-33.Williamson C, Geenes V. Intrahepatic cholestasis of pregnancy. Obstet Gynecol. 20J4 Jul; 124 (1): J20-33.Joshi D, James A, Quaglia A, Westbrook RH, Heneghan MA. Liver disease in pregnancy. Lancet. 2010 Feb 13. 375 (9714): 594-605.Joshi D, James A, Quaglia A, Westbrook RH, Heneghan MA. Liver disease in pregnancy. Lancet. 2010 Feb 13. 375 (9714): 594-605.Al Inizi S, Gupta R, Gale A: Fetal tachyarrhythmia with atrial flutter in obstetric cholestasis. Int J Gynaecol Obstet 2006; 93 (1): 53-4.Al Inizi S, Gupta R, Gale A: Fetal tachyarrhythmia with atrial flutter in obstetric cholestasis. Int J Gynaecol Obstet 2006; 93 (1): 53-4.Shand AW, Dickinson JE, D’Orsogna L: Refractory fetal supraventricular tachycardia and obstetric cholestasis. Fetal Diagn Ther 2008; 24 (3): 277-8J.Shand AW, Dickinson JE, D’Orsogna L: Refractory fetal supraventricular tachycardia and obstetric cholestasis. Fetal Diagn Ther 2008; 24 (3): 277-8J.Sheikh Abdul Kadir SH, Miragoli M, Abu-Hayyeh S, et al. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes. PLoS One 2010; 5: e9689.Sheikh Abdul Kadir SH, Miragoli M, Abu-Hayyeh S, et al. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes. PLoS One 2010; 5: e9689.Wang C, Chen X, Zhou SF, Li X. Impaired fetal adrenal function in intrahepatic cholestasis of pregnancy. Med Sci Monit. 2011; 17 (5): CR265-71.Wang C, Chen X, Zhou SF, Li X. Impaired fetal adrenal function in intrahepatic cholestasis of pregnancy. Med Sci Monit. 2011; 17 (5): CR265-71.Shi Y. Expression of pulmonary surfactant protein A mRNA in lungs of fetal rats with maternal intrahepatic cholestasis. Chinese journal of perinatal medicine. 2011; 14 (5).Shi Y. Expression of pulmonary surfactant protein A mRNA in lungs of fetal rats with maternal intrahepatic cholestasis. Chinese journal of perinatal medicine. 2011; 14 (5).Yu L, Ding YL, Wang CX. Relationship between total bile acid concentration and fetal pulmonary surfactant in intrahepatic cholestasis of pregnancy. Zhonghua Fu Chan Ke Za Zhi. 2011; 46 (5): 324-8.Yu L, Ding YL, Wang CX. Relationship between total bile acid concentration and fetal pulmonary surfactant in intrahepatic cholestasis of pregnancy. Zhonghua Fu Chan Ke Za Zhi. 2011; 46 (5): 324-8.Duhig K, Chappell LC, Shennan AH. Oxidative stress in pregnancy and reproduction. Obstet Med. 2016 Sep; 9 (3): 113-6.Duhig K, Chappell LC, Shennan AH. Oxidative stress in pregnancy and reproduction. Obstet Med. 2016 Sep; 9 (3): 113-6.Dobrzynski W, Trafikowska U, Trafikowska A, Pilecki A, Szymanski W, Zachara BA. Decreased selenium concentration in maternal and cord blood in preterm compared with term delivery. Analyst 1998; 123: 93-7.Dobrzynski W, Trafikowska U, Trafikowska A, Pilecki A, Szymanski W, Zachara BA. Decreased selenium concentration in maternal and cord blood in preterm compared with term delivery. Analyst 1998; 123: 93-7.Tara F, Rayman MP, Boskabadi H, et al. Selenium supplementation and premature (prelabour) rupture of membranes: a randomized double-blind placebo-controlled trial. J Obstet Gynaecol 2010; 30: 30-4.Tara F, Rayman MP, Boskabadi H, et al. Selenium supplementation and premature (prelabour) rupture of membranes: a randomized double-blind placebo-controlled trial. J Obstet Gynaecol 2010; 30: 30-4.Kilinc M, Guven MA, Ezer M, Ertas IE, Coskun A. Evaluation of serum selenium levels in Turkish women with gestational diabetes mellitus, glucose intolerants, and normal controls. Biol Trace Elem Res 2008; 123: 35-40.Kilinc M, Guven MA, Ezer M, Ertas IE, Coskun A. Evaluation of serum selenium levels in Turkish women with gestational diabetes mellitus, glucose intolerants, and normal controls. Biol Trace Elem Res 2008; 123: 35-40.Barrington JW, Lindsay P, James D, Smith S, Roberts A. Selenium deficiency and miscarriage: a possible link? Br J Obstet Gynaecol 1996; 103: 130-2.Barrington JW, Lindsay P, James D, Smith S, Roberts A. Selenium deficiency and miscarriage: a possible link? Br J Obstet Gynaecol 1996; 103: 130-2.Kocak I, Aksoy E, Ustun C. Recurrent spontaneous abortion and selenium deficiency. Int J Gynaecol Obstet 1999; 65: 79-80.Kocak I, Aksoy E, Ustun C. Recurrent spontaneous abortion and selenium deficiency. Int J Gynaecol Obstet 1999; 65: 79-80.Kauppila A, Korpela H, Makila UM, Yrjanheikki E. Low serum selenium concentration and glutathione peroxidase activity in intrahepatic cholestasis of pregnancy. Br Med J (Clin Res Ed) 1987; 294: 150-2.Kauppila A, Korpela H, Makila UM, Yrjanheikki E. Low serum selenium concentration and glutathione peroxidase activity in intrahepatic cholestasis of pregnancy. Br Med J (Clin Res Ed) 1987; 294: 150-2.Reyes H, Baez ME, Gonzalez MC, et al. Selenium, zinc and copper plasma levels in intrahepatic cholestasis of pregnancy, in normal pregnancies and in healthy individuals, in Chile. J Hepatol 2000; 32: 542-9.Reyes H, Baez ME, Gonzalez MC, et al. Selenium, zinc and copper plasma levels in intrahepatic cholestasis of pregnancy, in normal pregnancies and in healthy individuals, in Chile. J Hepatol 2000; 32: 542-9.Rayman MP. The importance of selenium to human health. Lancet 2000; 356: 233-41.Rayman MP. The importance of selenium to human health. Lancet 2000; 356: 233-41.Andozia MB, Vieira CS, Franceschini SA, Torqueti Tolloni MR, Silva de Sa MF, Ferriani RA. Ethinylestradiol and estradiol have different effects on oxidative stress and nitric oxide synthesis in human endothelial cell cultures. Fertil Steril. 2010; 94: 1578-82.Andozia MB, Vieira CS, Franceschini SA, Torqueti Tolloni MR, Silva de Sa MF, Ferriani RA. Ethinylestradiol and estradiol have different effects on oxidative stress and nitric oxide synthesis in human endothelial cell cultures. Fertil Steril. 2010; 94: 1578-82.Pincemail J, Vanbelle S, Gaspard U, Collette G, Haleng J, Cher-amy-Bien JP, et al. Effect of different contraceptive methods on the oxidative stress status in women aged 40-48 years from the ELAN study in the province of Liege, Belgium. Hum Reprod. 2007; 22: 2335-43.Pincemail J, Vanbelle S, Gaspard U, Collette G, Haleng J, Cher-amy-Bien JP, et al. Effect of different contraceptive methods on the oxidative stress status in women aged 40-48 years from the ELAN study in the province of Liege, Belgium. Hum Reprod. 2007; 22: 2335-43.Chen JT, Kotani K. Different Effects of Oral Contraceptive and Dy-drogesterone Treatment on Oxidative Stress Levels in Premenopausal Women. J Clin Med Res. 20J8 Feb; 10 (2): 146-153.Chen JT, Kotani K. Different Effects of Oral Contraceptive and Dy-drogesterone Treatment on Oxidative Stress Levels in Premenopausal Women. J Clin Med Res. 20J8 Feb; 10 (2): 146-153.

The authors declare that there are no conflicts of interest present.