nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical Universitynefr-182Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. EXPERIMENTAL INVESTIGATIONВлияние ингибиторов ангиотензин-превращающего фермента на уровень профиброгенных факторов роста в моче и морфологические изменения в паренхиме почек у крыс с инфицированным пузырно-мочеточниковым рефлюксомThe effect of angiotensin-converting enzyme inhibitors on urine level of profibrogenic growth factors and morphological changes in the renal parenchyma in rats with infected vesicoureteral refluxЗайковаНаталья М.ZaicovaN. M.nataliazaikova@mail.ruДлинВладимир ВикторовичDlinVladimir V.niki@pedklin.ruПетровичВержил ГеоргевичPetroviciVerjil G.petrovicivergil@yahoo.comСиницынаЛилия ВасильевнаSinitcinaLilia Vliliasinitsina@mail.ruКорсунскийАнатолий АлександровичKorsunschiiAnatolii A.dr_kaa@mail.ruГацканШтефан ГеоргиевичGatckanStefan G.stgatkan@mail.ruИнститут Матери и Ребенка; Первый Московский государственный медицинский университет им. И.М. СеченоваРоссияInstitution of Mother and Child Care; I.M. Sechenov First Moscow State Medical UniversityRussian FederationНаучно-исследовательский клинический институт педиатрии Российского научноисследовательского медицинского университета им. Н.И. ПироговаРоссияPirogov Russian National Research Medical UniversityRussian FederationИнститут Матери и РебенкаРоссияInstitution of Mother and Child CareRussian FederationПервый Московский государственный медицинский университет им. И.М. СеченоваРоссияI.M. Sechenov First Moscow State Medical UniversityRussian Federation2016010520162038595Copyright © Зайкова Н.М., Длин В.В., Петрович В.Г., Синицына Л.В., Корсунский А.А., Гацкан Ш.Г., 20162016Зайкова Н.М., Длин В.В., Петрович В.Г., Синицына Л.В., Корсунский А.А., Гацкан Ш.Г.Zaicova N.M., Dlin V.V., Petrovici V.G., Sinitcina L.V., Korsunschii A.A., Gatckan S.G.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/182

При экспериментальном инфицированном пузырно-мочеточниковом рефлюксе у крыс были установлены различные неоднотипные структурно-анатомические изменения со стороны почечно-мочеточникового комплекса на 1-, 3- и 6-м месяце эксперимента. Выраженность морфофункциональных изменений паренхимы почек взаимосвязана со степенью тяжести ПМР и длительностью воспалительного процесса в почечной ткани, что и определяет развитие тубулоинтерсти-циального фиброза. Высокий мочевой уровень Ang II и TGF-ß1 в моче у крыс, не получавших иАПФ, отражает выраженность склеротических изменений в почечной ткани. Раннее назначение иАПФ с целью блокады Ang II и ренопротекции снижает формирование фиброзной ткани в почках за счет снижения продукции фибробластами экстрацеллюлярного матрикса и профиброгенных факторов роста, но не влияет на уже сформировавшиеся очаги склероза.

In the experimental simulations bacterial vesico-ureteral reflux of rats, the results of the morphological studies at individuals gave us the possibility to identify various non-typical structural-anatomic changes in the renal-ureteral complex at 1, 3 and 6 months and to clarify the definite morphological status of the structural components of the kidneys at the individuals. The severity of the morphofunctional changes in renal parenchyma is interconnected with the severity and the duration of the VUR and the inflammatory process with the development of tubulointerstitial fibrosis. High levels of Ang II and TGF-ß1 in the urine of rats receiving no inhibitors reflects the severity of sclerotic changes in the renal tissue. Early administration of inhibitors for the purpose of the blockade of Ang II and renoprotection, reduce the formation of fibrosis tissue in the kidneys by reducing the production of extracellular matrix by fibroblasts and profibrogenic growth factors, but do not eliminate already formed foci sclerosis.

экспериментинфекция мочевых путейкрысыпузырно-мочеточниковый рефлюкстубулоинтерстициальный фиброзexperimenturinary tract infectionvesico-ureteral refluxratstubulointerstitial fibrosisReferencesGiovanni M, Kjell T, Hewitt I. Febrile Urinary Tract Infections in Children. New Engl J of Medicine 2011; 365:239-250Giovanni M, Kjell T, Hewitt I. Febrile Urinary Tract Infections in Children. New Engl J of Medicine 2011; 365:239-250Peters C, Rushton HG. Vesicoureteral reflux associated renal damage: congenital reflux nephropathy and acquired renal scarring. J Urol 2010;184(1):265-273Peters C, Rushton HG. Vesicoureteral reflux associated renal damage: congenital reflux nephropathy and acquired renal scarring. J Urol 2010;184(1):265-273Tej K. Mattoo. Vesicoureteral Reflux and Reflux Nephropathy. Adv Chronic Kidney Dis 2011; 18(5): 348-354Tej K. Mattoo. Vesicoureteral Reflux and Reflux Nephropathy. Adv Chronic Kidney Dis 2011; 18(5): 348-354Лакомова ДЮ, Стародубова АВ, Максимова АВ. Ранняя диагностика и прогнозирование развития нефросклероза у детей с пузырно-мочеточниковым рефлюксом. Bulletin of Medical Internet Conferences 2012: 2(1):27-28. [Lakomova DYU, Starodubova AV, Maksimova AV. Rannyaya diagnostika i prognozirovanie razvitiya nefroskleroza u detej s puzyrno-mochet-ochnikovym reflyuksom. Bulletin of Medical Internet Conferences 2012: 2(1):27-28]Лакомова ДЮ, Стародубова АВ, Максимова АВ. Ранняя диагностика и прогнозирование развития нефросклероза у детей с пузырно-мочеточниковым рефлюксом. Bulletin of Medical Internet Conferences 2012: 2(1):27-28. [Lakomova DYU, Starodubova AV, Maksimova AV. Rannyaya diagnostika i prognozirovanie razvitiya nefroskleroza u detej s puzyrno-mochet-ochnikovym reflyuksom. Bulletin of Medical Internet Conferences 2012: 2(1):27-28]North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Annual report. 2010. The EMMES Corporation, Rockville, MDNorth American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Annual report. 2010. The EMMES Corporation, Rockville, MDOh MM, Kim JW, Park MG et al. The impact of therapeutic delay time on acute scintigraphic lesion and ultimate scar formation in children with first febrile UTI. Eur J Pediatr 2012;171(3):565Oh MM, Kim JW, Park MG et al. The impact of therapeutic delay time on acute scintigraphic lesion and ultimate scar formation in children with first febrile UTI. Eur J Pediatr 2012;171(3):565Skoog SJ, Peters CA, Arant BS Jr et al. Pediatric Vesicoureteral Reflux Guidelines Panel Summary Report: Clinical Practice Guidelines for Screening Siblings of Children With Vesicoureteral Reflux and Neonates/Infants With Prenatal Hydronephrosis. J Urol 2010;184(3):1145-1151Skoog SJ, Peters CA, Arant BS Jr et al. Pediatric Vesicoureteral Reflux Guidelines Panel Summary Report: Clinical Practice Guidelines for Screening Siblings of Children With Vesicoureteral Reflux and Neonates/Infants With Prenatal Hydronephrosis. J Urol 2010;184(3):1145-1151Heather J. Lambert Primary, Nonsyndromic Vesicoureteric Reflux and Nephropathy in Sibling Pairs: A United Kingdom Cohort for a DNA Bank. CJASN, 2011; 6 (4 ) 760-766Heather J. Lambert Primary, Nonsyndromic Vesicoureteric Reflux and Nephropathy in Sibling Pairs: A United Kingdom Cohort for a DNA Bank. CJASN, 2011; 6 (4 ) 760-766Massanyi EZ, Preece J, Gupta A, et al. Utility of screening ultrasound after first febrile UTI among patients with clinically significant vesicoureteral reflux. Urology 2013;82(4):905Massanyi EZ, Preece J, Gupta A, et al. Utility of screening ultrasound after first febrile UTI among patients with clinically significant vesicoureteral reflux. Urology 2013;82(4):905Salo J, Ikäheimo R, Tapiainen T et al. Childhood urinary tract infections as a cause of chronic kidney disease. Pediatrics 2011;128(5):840Salo J, Ikäheimo R, Tapiainen T et al. Childhood urinary tract infections as a cause of chronic kidney disease. Pediatrics 2011;128(5):840Shaikh N, Ewing AL, Bhatnagar S et al. Risk of renal scarring in children with a first urinary tract infection: a systematic review. Pediatrics 2010;126:1084-1091Shaikh N, Ewing AL, Bhatnagar S et al. Risk of renal scarring in children with a first urinary tract infection: a systematic review. Pediatrics 2010;126:1084-1091Paltiel HJ, Mulkern RV, Perez-Atayde A et al. Effect of chronic, low-pressure, sterile vesicoureteral reflux on renal growth and function in a porcine model: a radiologic and pathologic study. Radiology 2000; 217(2):507-515Paltiel HJ, Mulkern RV, Perez-Atayde A et al. Effect of chronic, low-pressure, sterile vesicoureteral reflux on renal growth and function in a porcine model: a radiologic and pathologic study. Radiology 2000; 217(2):507-515Baek M, Paick SH, Jeong SJ et al. Urodynamic and histological changes in a sterile rabbit vesicoureteral reflux model. J Korean Med Sci 2010;25(9):1352-1358Baek M, Paick SH, Jeong SJ et al. Urodynamic and histological changes in a sterile rabbit vesicoureteral reflux model. J Korean Med Sci 2010;25(9):1352-1358Slotki IN, Asscher AW. Prevention of renal scarring in experimental pyelonephritis in the rat by early antibiotic therapy. Nephron 1982;30:262-268Slotki IN, Asscher AW. Prevention of renal scarring in experimental pyelonephritis in the rat by early antibiotic therapy. Nephron 1982;30:262-268Roberts JA, Kaack MB, Baskin G. Treatment of experimental pyelonephritis in the monkey. J Urol 1990;143(1):150-154Roberts JA, Kaack MB, Baskin G. Treatment of experimental pyelonephritis in the monkey. J Urol 1990;143(1):150-154Silva AC, Flynn JT. The rennin-angiotensin-aldosteron system in 2011: role in hypertension and chronic kidney disease. Pediatr Nephrol 2012. DOI 10.10007/s0046-011-2002Silva AC, Flynn JT. The rennin-angiotensin-aldosteron system in 2011: role in hypertension and chronic kidney disease. Pediatr Nephrol 2012. DOI 10.10007/s0046-011-2002Hussein A, Askar E, Elsaeid M, Schaefer F. Functional polymorphisms in transforming growth factor-beta-1 (TGFbeta-1) and vascular endothelial growth factor (VEGF) genes modify risk of renal parenchymal scarring following childhood urinary tract infection. Nephrol Dial Transplant 2010;25:779-785Hussein A, Askar E, Elsaeid M, Schaefer F. Functional polymorphisms in transforming growth factor-beta-1 (TGFbeta-1) and vascular endothelial growth factor (VEGF) genes modify risk of renal parenchymal scarring following childhood urinary tract infection. Nephrol Dial Transplant 2010;25:779-785Hussein A, Askar E, Elsaeid M, Schaefer F. Functional polymorphisms in transforming growth factor-beta-1 (TGFbeta-1) and vascular endothelial growth factor (VEGF) genes modify risk of renal parenchymal scarring following childhood urinary tract infection. Nephrol Dial Transplant 2010;25(3):779-785Hussein A, Askar E, Elsaeid M, Schaefer F. Functional polymorphisms in transforming growth factor-beta-1 (TGFbeta-1) and vascular endothelial growth factor (VEGF) genes modify risk of renal parenchymal scarring following childhood urinary tract infection. Nephrol Dial Transplant 2010;25(3):779-785Меркоданова ЮА, Утц ИА. Цитокиновый профиль мочи при различных этиопатогенетических вариантах хронического пиелонефрита у детей. Саратовск науч-мед журн 2011; 7(4): 901-904 [Merkodanova ΥA, Utts IА. Titokinovii profil mohi pri razlichnih ehtiopatogeneticheskih variantah khronicheskogo pielonefrita u detei. Saratovskii nauchno-meditsinskii jurnal 2011; 7(4): 901-904]Меркоданова ЮА, Утц ИА. Цитокиновый профиль мочи при различных этиопатогенетических вариантах хронического пиелонефрита у детей. Саратовск науч-мед журн 2011; 7(4): 901-904 [Merkodanova ΥA, Utts IА. Titokinovii profil mohi pri razlichnih ehtiopatogeneticheskih variantah khronicheskogo pielonefrita u detei. Saratovskii nauchno-meditsinskii jurnal 2011; 7(4): 901-904]Ibragim Gokce, Harica Alpay, Nese Biykli et al. Urinary levels of interleikin-6 and interleikin-8 in patients with vesicoureteral reflux and renal parenchymal scar. Peadiatr Nephrol 2010; 25:905-912Ibragim Gokce, Harica Alpay, Nese Biykli et al. Urinary levels of interleikin-6 and interleikin-8 in patients with vesicoureteral reflux and renal parenchymal scar. Peadiatr Nephrol 2010; 25:905-912Morales MG, Vazquez Y Acuna MJ, Rivera JC, Simon F. Angiotensin II-induced pro-fibrotic effects require p38MAPK activity and transforming growth factor beta 1 expression in skeletal muscle cells. Int J Biochem Cell Biol 2012 Nov;44(11):1993-2002Morales MG, Vazquez Y Acuna MJ, Rivera JC, Simon F. Angiotensin II-induced pro-fibrotic effects require p38MAPK activity and transforming growth factor beta 1 expression in skeletal muscle cells. Int J Biochem Cell Biol 2012 Nov;44(11):1993-2002Rizvi S, Raza ST, Mahdi F. Association of genetic variants with diabetic nephropathy. World J Diabetes 2014: 15;5(6):809-186Rizvi S, Raza ST, Mahdi F. Association of genetic variants with diabetic nephropathy. World J Diabetes 2014: 15;5(6):809-186Huo P, Zhang D, Guan X et al. Association between genetic polymorphisms of ACE & eNOS and diabetic nephropathy. Mol Biol Rep 2015;42(1):27-33Huo P, Zhang D, Guan X et al. Association between genetic polymorphisms of ACE & eNOS and diabetic nephropathy. Mol Biol Rep 2015;42(1):27-33Мачехина ЛЮ. Современные взгляды на патогенетические механизмы, течение, прогноз и методы лечения рефлюкс-нефропатии: Автореф. дис.. канд. мед. наук. М., 2010; 38 с. [Machehina LU. Sovremennie vzgliadi na patogeneticheskie mehanizmi, tehenie, prognoz i metodi lechenia refluks-nefropatii. Аvtor. diss. na sosk. uh. step. kand. med. nauk, Moskva, 2010, 38 s]Мачехина ЛЮ. Современные взгляды на патогенетические механизмы, течение, прогноз и методы лечения рефлюкс-нефропатии: Автореф. дис.. канд. мед. наук. М., 2010; 38 с. [Machehina LU. Sovremennie vzgliadi na patogeneticheskie mehanizmi, tehenie, prognoz i metodi lechenia refluks-nefropatii. Аvtor. diss. na sosk. uh. step. kand. med. nauk, Moskva, 2010, 38 s]Паунова СС, Ольхова ЕБ. Оценка эффективности ингибиторов АПФ у детей с пузырно-мочеточниковым рефлюксом методом допплеровского исследования ренального кровотока. Материалы 1 Всероссийского конгресса «Современные технологии в педиатрии и детской хирургии. М., 2002; 399-400. [Paunova SS, Olhova EB. Otenka effektivnosti ingibitorov APF u detei s puzyrno-mohetochnikovim refluksom metodom dopplerovskogo issledovania renalnogo krovotoka. Materiali 1 Vserossiiskogo kongressa «Sovremennie tehnologii v pediatrii i detskoi hirurgii. Moskva, 2002. S. 399-400]Паунова СС, Ольхова ЕБ. Оценка эффективности ингибиторов АПФ у детей с пузырно-мочеточниковым рефлюксом методом допплеровского исследования ренального кровотока. Материалы 1 Всероссийского конгресса «Современные технологии в педиатрии и детской хирургии. М., 2002; 399-400. [Paunova SS, Olhova EB. Otenka effektivnosti ingibitorov APF u detei s puzyrno-mohetochnikovim refluksom metodom dopplerovskogo issledovania renalnogo krovotoka. Materiali 1 Vserossiiskogo kongressa «Sovremennie tehnologii v pediatrii i detskoi hirurgii. Moskva, 2002. S. 399-400]Лопухин ЮМ. Экспериментальная хирургия. М.: Медицина, 1971, 224 с. - прототип [Lopukhin YM. Eksperimentalnaa hirurgia. M.: Meditsina, 1971, s.224 - prototip]Лопухин ЮМ. Экспериментальная хирургия. М.: Медицина, 1971, 224 с. - прототип [Lopukhin YM. Eksperimentalnaa hirurgia. M.: Meditsina, 1971, s.224 - prototip]Khalil A, Tullus K, Bakhiet M et al. Angiotensin II type I receptor antagonist (Losartan) down regulates transforming growth factor-β in experimental acute pyelonephritis. J Urol 2000;164:186-191Khalil A, Tullus K, Bakhiet M et al. Angiotensin II type I receptor antagonist (Losartan) down regulates transforming growth factor-β in experimental acute pyelonephritis. J Urol 2000;164:186-191Rodriguez-Iturbe B, Quiroz Y Shahrarami A et al. Myco-phenole mofetil ameliorates nephropathy in the obese Zucker rat. Kidney Int 2005:68:1041-1047Rodriguez-Iturbe B, Quiroz Y Shahrarami A et al. Myco-phenole mofetil ameliorates nephropathy in the obese Zucker rat. Kidney Int 2005:68:1041-1047Peter J. Margetts, Catherine Hoff, Limin Liu. Transforming growth factor β-induced peritoneal fibrosis is mouse strain dependent. Oxford Journals Medicine Nephrology Dialysis Transplantation 2012 :28(8): 2015-2027Peter J. Margetts, Catherine Hoff, Limin Liu. Transforming growth factor β-induced peritoneal fibrosis is mouse strain dependent. Oxford Journals Medicine Nephrology Dialysis Transplantation 2012 :28(8): 2015-2027Gawlowska-Marciniak A, Niedzielski JK. Evaluation of TGF-ß1, CCL5/RANTES and sFas/Apo-1 urine concentration in children with ureteropelvic junction obstruction. Arch Med Sci 2013; 9(5): 888-894Gawlowska-Marciniak A, Niedzielski JK. Evaluation of TGF-ß1, CCL5/RANTES and sFas/Apo-1 urine concentration in children with ureteropelvic junction obstruction. Arch Med Sci 2013; 9(5): 888-894Kagami S, Border WA, Miller DE et al. Angiotensin II stimulates extracellular matrix protein synthesis through induction of TGF-ß1 expression in rat glomerular mesangial cells. J Clin Invest 1994; 93:2431-2437Kagami S, Border WA, Miller DE et al. Angiotensin II stimulates extracellular matrix protein synthesis through induction of TGF-ß1 expression in rat glomerular mesangial cells. J Clin Invest 1994; 93:2431-2437Serlachius E, Sundelin B, Eklof A. Pyelonephritis provokes growth retardation and apoptosis in infant rat renal cortex. Kidney Int 1997;51:1855-1862Serlachius E, Sundelin B, Eklof A. Pyelonephritis provokes growth retardation and apoptosis in infant rat renal cortex. Kidney Int 1997;51:1855-1862Liang XL. Beyond Early Diagnosis: Prognostic Biomarkers for Monitoring Acute Kidney Injury: X.-L. Liang, W. Shi. Hong Kong J Nephrol 2010; 12(2):45-49Liang XL. Beyond Early Diagnosis: Prognostic Biomarkers for Monitoring Acute Kidney Injury: X.-L. Liang, W. Shi. Hong Kong J Nephrol 2010; 12(2):45-49Singal AK, Bajpai M, Dinda AK. Blockade of rennin-аngiotensin system blunts the fibrotic response in experimental acute pyelonephritis. J of Indian Assot of pediat Surgeons Year 2005;10 (1):20-24Singal AK, Bajpai M, Dinda AK. Blockade of rennin-аngiotensin system blunts the fibrotic response in experimental acute pyelonephritis. J of Indian Assot of pediat Surgeons Year 2005;10 (1):20-24

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