nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.24884/1561-6274-2005-9-4-67-74nefr-724Research ArticleЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯГИПЕРГОМОЦИСТЕИНЕМИЯ УСУГУБЛЯЕТ ПОВРЕЖДЕНИЯ НЕФРОНА ПРИ ЭКСПЕРИМЕНТАЛЬНОЙ ХРОНИЧЕСКОЙ ПОЧЕЧНОЙ НЕДОСТАТОЧНОСТИHYPERHOMOCYSTEINEMIA EXACERBATES THE NEPHRON INJURIES INDUCED BY EXPERIMENTAL KIDNEY FAILUREСмирновА. В.SmirnovA. V.

Научно-исследовательский центр, кафедра патологической физилогии

ДобронравовВ. А.DobronravovV. A.

Научно-исследовательский центр, кафедра патологической физилогии

НеворотинА. И.NevorotinA. I.

Научно-исследовательский центр, кафедра патологической физилогии

ХохловС. Е.KhokhlovS. E.

Научно-исследовательский центр, кафедра патологической физилогии

СиповскийВ. Г.SipovskyV. G.

Научно-исследовательский центр, кафедра патологической физилогии

БарабановаВ. В.BarabanovaV. V.

Научно-исследовательский центр, кафедра патологической физилогии

ЧефуС. Г.ChefuS. G.

Научно-исследовательский центр, кафедра патологической физилогии

ЖлобаА. А.ZhlobaA. A.

Научно-исследовательский центр, кафедра патологической физилогии

БлашкоЭ. Л.BlashkoE. L.

Научно-исследовательский центр, кафедра патологической физилогии

Научно-исследовательский институт нефрологии, Cанкт-Петербургский государственный медицинский университет имени акад. И.П. ПавловаRussian Federation200510042005946774Copyright © Смирнов А.В., Добронравов В.А., Неворотин А.И., Хохлов С.Е., Сиповский В.Г., Барабанова В.В., Чефу С.Г., Жлоба А.А., Блашко Э.Л., 20052005Смирнов А.В., Добронравов В.А., Неворотин А.И., Хохлов С.Е., Сиповский В.Г., Барабанова В.В., Чефу С.Г., Жлоба А.А., Блашко Э.Л.Smirnov A.V., Dobronravov V.A., Nevorotin A.I., Khokhlov S.E., Sipovsky V.G., Barabanova V.V., Chefu S.G., Zhloba A.A., Blashko E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/724

ЦЕЛЬ ИССЛЕДОВАНИЯ – оценить возможный вклад гомоцистеина в развитие повреждений клубочков и проксимальных канальцев (ПК) в условиях экспериментальной хронической почечной недостаточности (ПН). МАТЕРИАЛ И МЕТОДЫ. Использовали крыс линии Вистар, которые были подвергнуты субтотальной нефрэктомии. Экспериментальной группе животных (n=11) после операции вводили гомоцистеин (ГЦ) в дозе 13,4 мг/кг внутримышечно. В качестве контрольной группы использовали нефрэктомированных животных без последующего введения ГЦ (n=10). В обеих группах определяли концентрацию общего ГЦ, креатинина, мочевины плазмы крови, а также суточный диурез, концентрацию альбумина и креатинина мочи с последующим расчетом отношения альбумин/креатинин (ACR), концентрационного индекса (Ucr/Pcr) и клиренса креатинина (Ccr). Проводили светооптическое и электронномикроскопическое исследование почек. РЕЗУЛЬТАТЫ. Общий ГЦ плазмы крови составил 5,0±0,7 μ моль/л и 7,7±1,5 μ моль/л в контрольной и экспериментальной группах соответственно (p < 0.005). У экспериментальных животных в сравнении с контрольными были выше значения logACR на 100 г массы (2,12±0,52 vs 1,43±0,32 мг/г, p <0 .025), креатинина плазмы (79,0±13,9 vs 56,3±8,0 μ моль/л, p < 0.001) и ниже Ccr (0,20±0,07 vs 0,46±0,08 мл/мин, p < 0.005) и Ucr/Pcr (53,2±25,9 vs 123,3±25,7, p <0 .005). Морфологически в контрольной группе крыс выявлены умеренная мезангиальная пролиферация и адгезия лейкоцитов к эндотелию капилляров клубочков наряду с выраженным нарастанием количества структур, отражающих эндоцитоз, включая большие апикальные вакуоли в клетках ПК. Назначение ГЦ приводило к усугублению описанных повреждений в обоих отделах нефрона, а также к депозиции фибрина в просвете капилляров и выраженной дезорганизации базальной цитоплазмы клеток ПК. ЗАКЛЮЧЕНИЕ. Результаты светооптического и субмикроскопического анализа в сочетании с биохимическими данными рассматривают ся как прямое свидетельство дополнительного повреждающего воздействия ГГЦ на основные клеточные популяции не фрона в условиях экспериментальной ПН.

THE AIM of the investigation was to evaluate a possible impact of homocysteine (HCy) on the glomerular and proximal tubule cell injury in the remnant kidney model (RKM). MATERIAL AND METHODS. An experimental group of adult male albino Wistar rats underwent subtotal nephrectomy followed by daily administration of HCy (i.m., 13.4 mg/kg) for three weeks (n=11). Nephrectomized rats not given HCy were used as a control group (n=11). Routine blood and urine functional tests as well as light and electron microscopic examinations of the kidney samples were used to compare urine albumincreatinine ratio (ACR), creatinine clearance (Ccr) and cell alterations in RKM alone and those with a combination of RKM and superimposed hyperhomocysteinemia. RESULTS. Total plasma HCy was 5.0±0.7 and 7.7±1.5 in control and experimental animals respectively (p< 0.005). In the experimental group an increased logACR per 100 g of body mass (2.12±0.52 vs 1.43±0.32 mg/g, p<0.025) and plasma creatinine concentration (79.0±13.9 vs 56.3±8.0, p< 0.001) and decreased Ccr (0.20±0.7 vs 0.46±0.08 ml/min, p<0.005) and Ucr/Pcr (53.2±25.9 vs 123±25.7, p<0.005) were observed as compared to the control group. Moderate mesangial cell proliferation and local leukocyte adhesion to the endothelial lining in the glomeruli, with a pronounced increase of the amount of endocytosislabeling structures, large apical vacuoles included, in the proximal tubule cells, were registered in the kidney parenchyma of the RKM rats. Administration of HCy apparently aggravated the above mentioned alterations in both nephron compartments and also resulted in fibrin deposition within the glomerular capillaries and extensive disorganization of the basal cytoplasm in the proximal tubule cells. CONCLUSION. Both light and electron microscopic data reinforced by the appropriate biochemical findings are considered as a direct evidence of the additional deleterious effects of HCy on the major cell populations of the nephron under conditions of experimental renal failure.

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