arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2014-20-6-522-530arthyper-156Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯORIGINAL ARTICLEПОЧЕЧНАЯ ЭКСПРЕССИЯ БЕЛКА ΑKLOTHO АССОЦИИРОВАНА С ГИПЕРТРОФИЕЙ МИОКАРДА (ЭКСПЕРИМЕНТАЛЬНОЕ ИССЛЕДОВАНИЕ)RENAL ΑKLOTHO EXPRESSION IS ASSOCIATED WITH MYOCARDIAL HYPERTROPHY (EXPERIMENTAL STUDY)БогдановаЕ. О.BogdanovaE. O.

Младший научный сотрудник Научно-исследовательского института (НИИ) нефрологии ГБОУ ВПО ПСПбГМУ им. И. П. Павлова.

Контактная информация: Богданова Евдокия Олеговна, НИИ нефрологии, ГБОУ ВПО ППбГМУ им. И.П. Павлова , ул. Л. Толстого, д. 17, Санкт-Петербург, Россия, 197101. Тел.: +7(812)234–66–56. Факс: +7(812)234–95–63. E-mail: evdokia.bogdanova@gmail.com

 

Junior Researcher, Research Institute of Nephrology

БересневаО. Н.SemenovaN. Yu.

Junior Researcher

evdokia.bogdanova@gmail.comСеменоваН. Ю.BeresnevaO. N.

PhD, Biology Sciences, Senior Researcher, Center of Laboratory Diagnostics

evdokia.bogdanova@gmail.comПарастаеваМ. М.ParastaevaM. M.

PhD, Biology Sciences, Senior Researcher, Laboratory of Clinical Physiology of Kidneys, Research Institute of Nephrology

evdokia.bogdanova@gmail.comИвановаГ. Т.IvanovaG. T.

Кандидат биологических наук, старший научный сотрудник Института физиологии имени И. П. Павлова Российской академии наук

PhD, Biology Sciences, Senior Researcher

evdokia.bogdanova@gmail.comГалкинаО. В.GalkinaO. V.

PhD, Biology Sciences, Associate Professor, Head, Laboratory of Biochemical Homeostatis, Research Institute of Nephrology

evdokia.bogdanova@gmail.comЗубинаИ. М.ZubinaI. M.

PhD, Biology Sciences, Senior Researcher, Laboratory of Biochemical Homeostatis, Research Institute of Nephrology

evdokia.bogdanova@gmail.comКаюковИ. Г.KayukovI. G.

MD, PhD, DSc, Professor, Head, Laboratory of Clinical Physiology of Kidneys, Research Institute of Nephrology

evdokia.bogdanova@gmail.comКоваленкоТ. Л.KovalenkoT. L.

Center of Laboratory Diagnostics

evdokia.bogdanova@gmail.comКотенкоЛ. В.KotenkoL. V.

Head, Biochemical Laboratory, Center of Laboratory Diagnostics

evdokia.bogdanova@gmail.comДобронравовВ. А.DobronravovV. A.

MD, PhD, DSc, Professor, Department of the Propaedeutics of Internal Diseases, Deputy Director on Research, Research Institute of Nephrology

evdokia.bogdanova@gmail.comПервый Санкт-Петербургский государственный медицинский университет имени академика И.П.Павлова, Санкт-ПетербургРоссияResearch Institute of Nephrology at First Pavlov State Medical University of St. Petersburg, St PetersburgRussian FederationПервый Санкт-Петербургский государственный медицинский университет имени академика И.П.Павлова, Санкт-ПетербургРоссияRussian Research Institute of Hematology and Transfusiology, St PetersburgRussian FederationЛаборатория по изучению лейкозов Российского научно-исследовательского института гематологии и трансфузиологии, Санкт-ПетербургРоссияResearch Institute of Nephrology at First Pavlov State Medical University of St. Petersburg, St PetersburgRussian FederationИнститут физиологии имени И. П. Павлова Российской академии наук, Санкт-ПетербургРоссияPavlov Institute of Physiology of Russian Academy of Sciences, St PetersburgRussian FederationЦентр лабораторной диагностики Государственного бюджетного образовательного учреждения высшего профессионального образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской Федерации, Санкт-ПетербургРоссияResearch Institute of Nephrology at First Pavlov State Medical University of St. Petersburg, St PetersburgRussian Federation201406032015206522530Copyright © Богданова Е.О., Береснева О.Н., Семенова Н.Ю., Парастаева М.М., Иванова Г.Т., Галкина О.В., Зубина И.М., Каюков И.Г., Коваленко Т.Л., Котенко Л.В., Добронравов В.А., 20152015Богданова Е.О., Береснева О.Н., Семенова Н.Ю., Парастаева М.М., Иванова Г.Т., Галкина О.В., Зубина И.М., Каюков И.Г., Коваленко Т.Л., Котенко Л.В., Добронравов В.А.Bogdanova E.O., Semenova N.Y., Beresneva O.N., Parastaeva M.M., Ivanova G.T., Galkina O.V., Zubina I.M., Kayukov I.G., Kovalenko T.L., Kotenko L.V., Dobronravov V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/156

гипотезы о наличии возможной связи между изменениями в системе фактор роста фибробластов 23 (FGF23)/αKlotho и прогрессированием гипертрофии миокарда на ранних стадиях формирования дисфункции почек (ДП).

Материалы и методы

Материалы и методы. Для моделирования ДП выполняли резекцию 3/4 и 5/6 почечной ткани у крыс линии SHR, сроки эксперимента — 1 и 2 месяца. В качестве контроля использовали ложнооперированных животных. Анализировали индекс массы миокарда (ИММ), содержание белка αKlotho в тубулярном эпителии (иммуногистохимическим методом), концентрации FGF23, интактного паратиреоидного гормона (iPTH) в сыворотке крови (иммуноферментный анализ), а также неорганического фосфата (Pi), натрия, креатинина в сыворотке крови и моче, концентрации белка в моче.

Результаты

Результаты. Реализованные модели соответствуют клиническим стадиям 1–3 хронической болезни почек. Почечная экскреция Pi увеличивается в группах животных, подвергнутых нефрэктомии. По мере нарастания степени повреждения почек и увеличения ИММ существенных изменений концентраций FGF23 и iРТН в сыворотке крови не выявлено, в то время как содержание белка αKlotho в почке значительно снижалось. При мультивариантном анализе показана значимая обратная связь между ИММ и содержанием αKlotho в почке, независимая от влияния других исследуемых факторов, включая уровень артериального давления и степень снижения функции почек.

Выводы

Выводы. Содержание белка αKlotho в тубулярном эпителии почки ассоциировано с ИММ, что позволяет предположить участие αKlotho в механизмах ремоделирования миокарда в условиях персистирования артериальной гипертензии и ДП.

Objective

Objective. The study was aimed to test a hypothesis on possible connection between αKlotho and (or) fibroblast growth factor 23 (FGF23) and myocardial hypertrophy at early stages of the renal dysfunction (RD).

Design and methods

Design and methods. Experimental models of chronic kidney injury were 3/4 or 5/6 nephrectomy (NE) in SHR rats. Sham-operated SHR rats were used as control. The timing of experiments was one or two months to achieve an expected fall of glomerular filtration rate (GFR) corresponding to early stages of RD. αKlotho protein in tubular epithelium was detected by immunohistochemistry. Serum concentrations of FGF23 and intact parathyroid hormone (iPTH), serum and urine levels of inorganic phosphate (Pi), Na, creatinine and protein as well as myocardial mass index (MMI) were measured.

 Results

 Results. Implemented models of RD corresponded to 1C–3C stages of human chronic kidney disease. Renal excretion of Pi significantly increased in the groups of nephrectomized animals. No significant differences were observed in serum concentrations of FGF23 and iPTH whereas the renal αKlotho expression decreases along with an increasing degree of kidney injury and MMI. The significant negative association between MMI and the renal αKlotho expression was independent of other potential confounders as confirmed by a multivariate regression analysis.

Conclusions

Conclusions. The obtained experimental data suggest that αKlotho can participate in mechanisms of myocardial remodeling in persistent hypertension and RD.

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