nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.36485/1561-6274-2019-236-83-91nefr-1772Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. EXPERIMENTAL INVESTIGATIONИнгибиторы канонического сигнального пути Wnt и нарушение обмена неорганического фосфата при экспериментальной дисфункции почекInhibitors of canonical Wnt signaling pathway and inorganic phosphate imbalance in experimental chronic kidney diseasehttps://orcid.org/0000-0003-1969-1959БогдановаЕ. О.BogdanovaE. O.

Богданова Евдокия Олеговна, кандидат биологических наук, Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, Научно-исследовательский институт нефрологии, лаборатория биохимического гомеостаза, младший научный сотрудник

197022, Санкт-Петербург, ул. Л. Толстого, д. 17, корп. 54

Evdokia O. Bogdanova, PhD, Pavlov First Saint Petersburg State Medical University, Research Institute of Nephrology, Laboratory of Biochemical Homeostasis

197022, St. Petersburg, L. Tolstoy st., 17, build. 54

evdokia.bogdanova@gmail.comhttps://orcid.org/0000-0002-7532-2405БересневаО. Н.BeresnevaO. N.

Береснева Ольга Николаевна, кандидат биологических наук, Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, Научно-исследовательский институт нефрологии, лаборатория клинической физиологии почек, старший научный сотрудник

197022, Санкт-Петербург, ул. Л. Толстого, д. 17, корп. 54

Olga N. Beresneva, PhD, senior researcher, Pavlov First Saint Petersburg State Medical University, Research Institute of Nephrology, Laboratory of Clinical Physiology of the Kidney

197022, St. Petersburg, L. Tolstoy st., 17, build. 54

beresnevaolga@list.ruЗубинаИ. М.ZubinaI. M.

Зубина Ирина Михайловна, кандидат биологических наук, Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, Научно-исследовательский институт нефрологии, лаборатория биохимического гомеостаза

197022, Санкт-Петербург, ул. Л. Толстого, д. 17

Irina M. Zubina, PhD in Biology, Pavlov First Saint Petersburg State Medical University, Research Institute of Nephrology, Laboratory of Biochemical Homeostasis

197022, St. Petersburg, L. Tolstoy st., 17, build. 54

zubina@list.ruИвановаГ. Т.IvanovaG. T.

Иванова Галина Тажимовна, кандидат биологических наук, лаборатория физиологии сердечно-сосудистой и лимфатической систем, старший научный сотрудник

199034, Санкт-Петербург, наб. Макарова, д. 6.

Galina T. Ivanova, PhD, senior researcher, Laboratory of physiology of cardiovascular and lymphatic systems

199034, St. Petersburg, Makarova Emb., 6,

tazhim@list.ruПарастаеваМ. М.ParastaevaM. M.

Парастаева Марина Магрезовна, кандидат биологических наук, Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, Научнои-сследовательский институт нефрологии, лаборатория клинической физиологии почек, старший научный сотрудник

197022, Санкт-Петербург, ул. Л. Толстого, д. 17, корп. 54

Marina M. Parastaeva, PhD, senior researcher, Pavlov First Saint Petersburg State Medical University, Research Institute of Nephrology, Laboratory of Clinical Physiology of the Kidney

197022, St. Petersburg, L. Tolstoy st., 17, build. 54

parastaeva@list.ruhttps://orcid.org/0000-0001-7265-7392ГалкинаО. В.GalkinaO. V.

Галкина Ольга Владимировна, кандидат биологических наук,  Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, Научно-исследовательский институт нефрологии, заведующая лабораторией биохимического гомеостаза

197022, Санкт-Петербург, ул. Л. Толстого, д. 17

Olga V. Galkina, PhD in Biology, Pavlov First Saint Petersburg State Medical University, Research Institute of Nephrology, Head of The Laboratory of Biochemical Homeostasis

197022, St. Petersburg, L. Tolstoy st., 17, build. 54

ovgalkina@mail.ruhttps://orcid.org/0000-0003-0793-5629КаюковИ. Г.KayukovI. G.

Каюков Иван Глебович, профессор, доктор медицинских наук, Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, Научно-исследовательский институт нефрологии, руководитель лаборатории клинической физиологии почек

197022, Санкт-Петербург, ул. Л. Толстого, д. 17, корп. 54

Ivan G. Kayukov, Prof.,  MD, PhD, DMedSci, Pavlov First Saint Petersburg State Medical University, Research Institute of Nephrology, Head of The Laboratory of Clinical Physiology of the Kidney

197022, St. Petersburg, L. Tolstoy st., 17, build. 54

kvaka55@mail.ruhttps://orcid.org/0000-0002-7179-5520ДобронравовВ. А.DobronravovV. A.

Добронравов Владимир Александрович, профессор, доктор медицинских наук, Первый Санкт-Петербургский государственныймедицинский университет им. акад. И.П. Павлова, заместитель директора Научно-исследовательского института нефрологии по научной работе

197022, Санкт-Петербург, ул. Л. Толстого, д. 17, корп. 54

Vladimir A. Dobronravov, Prof.,  MD, PhD, DMedSci, Pavlov First Saint Petersburg State Medical University, Research Institute of Nephrology, Vice-Director

197022, St. Petersburg, L. Tolstoy st., 17, build. 54

dobronravov@nephrolog.ruПервый Санкт-Петербургский государственный медицинский университет им. акад. И.П. ПавловаРоссияPavlov First Saint-Petersburg State Medical UniversityRussian FederationИнститут физиологии им. И.П. Павлова РАНРоссияI.P. Pavlov Institute of Physiology Russian Academy of ScienceRussian Federation2019251220192368391Copyright © Богданова Е.О., Береснева О.Н., Зубина И.М., Иванова Г.Т., Парастаева М.М., Галкина О.В., Каюков И.Г., Добронравов В.А., 20192019Богданова Е.О., Береснева О.Н., Зубина И.М., Иванова Г.Т., Парастаева М.М., Галкина О.В., Каюков И.Г., Добронравов В.А.Bogdanova E.O., Beresneva O.N., Zubina I.M., Ivanova G.T., Parastaeva M.M., Galkina O.V., Kayukov I.G., 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://journal.nephrolog.ru/jour/article/view/1772ВВЕДЕНИЕ

ВВЕДЕНИЕ. Молекулярные механизмы начальных стадий нарушений обмена неорганического фосфата (Pi) при хронической болезни почек (ХБП) остаются недостаточно изученными.

ЦЕЛЬ ИССЛЕДОВАНИЯ

ЦЕЛЬ ИССЛЕДОВАНИЯ: проверка гипотезы об изменении образования ингибиторов канонического сигнального пути Wnt и снижении костного обмена как одном из ранних механизмов нарушения баланса Pi при ХБП.

МАТЕРИАЛ И МЕТОДЫ

МАТЕРИАЛ И МЕТОДЫ. У крыс линии SHR (N=52) – животные с нефрэктомией (NE) или ложной операцией (SO) и сроками наблюдения 2, 4 и 6 мес, измеряли концентрации креатинина (Cr), неорганического фосфата (Pi) и паратиреоидного гормона (PTH), фактора роста фибробластов 23 (FGF23), остеопротегерина (OPG), склеростина (SOST) и Dickkopf-1 (DKK) в сыворотке крови, экспрессию мРНК генов SOST и DKK в почке, альбуминурию (Alb), протеинурию (uTP), фракционную (FEPi) и абсолютную (uPi24) экскрецию Pi. РЕЗУЛЬТАТЫ. Экспериментальная модель была сопоставима с 1–2 стадиями ХБП. В группах NE4 и NE6 концентрация sPi и его экскреция почками (FEPi и uPi24) были значительно выше, чем у соответствующего контроля SO4 (p=0,006, p<0,010) и SO6 (p=0,002, p=0,028). Концентрации FGF23 и PTH в сыворотке NE и SO животных достоверно не различались. В группах NE4 и NE6 концентрации SOST и DKK в сыворотке были значительно выше, чем у контроля (p<0,049, p<0,043), при этом экспрессия генов SOST и DKK в NE почке снижалась или не изменялась значительно. Концентрация OPG была выше в группе NE6 при сравнении с SO6 (p=0,028).

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Начальные стадии экспериментальной ХБП характеризует повышение концентраций Dikkopf-1, склеростина, а также остеопротегерина в сыворотке крови. Полученные данные позволяют предполагать возможную роль ингибирования канонического Wnt-сигналинга и редукции обмена кости на ранних стадиях патогенеза нарушений обмена Pi при ХБП.

BACKGROUND

BACKGROUND. The molecular mechanisms of the initial stages of inorganic phosphate (Pi) metabolic disorders in chronic kidney disease (CKD) remain poorly understood.

THE AIM

THE AIM. To test the hypothesis about changes in canonical Wnt signaling pathway inhibitors biosynthesis and a concomitant decrease in bone turnover as one of early mechanisms of Pi imbalance in CKD.

MATERIAL AND METHODS

MATERIAL AND METHODS. Creatinine (Cr), inorganic phosphate (Pi), serum parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), sclerostin (SOST) and Dickkopf-1 (DKK), renal SOST and DKK mRNA expression, albuminuria (Alb), proteinuria (uTP) levels, fractional (FEPi) and daily (uPi24) Pi excretion were analyzed in SHR rats (N = 52) with 3/4 nephrectomy (NE) or sham operation (SO) and observation periods of 2, 4, and 6 months.

RESULTS

RESULTS. Experimental model was comparable with 1-2 stages of CKD. In groups NE4 and NE6, the concentration of sPi and renal Pi excretion (FEPi and uPi24) were significantly higher vs corresponding controls SO4 (p = 0.006, p <0.010) and SO6 (p = 0.002, p = 0.028). Serum concentrations of FGF23 and PTH in NE and SO animals did not change significantly. In NE4 and NE6 groups, serum SOST and DKK concentrations were significantly higher vs controls (p <0.049, p <0.043), while the kidney expression SOST and DKK mRNA in NE rats did not change significantly or decreased (p = 0.002, p <0.011). The serum concentration of OPG was higher in the NE6 vs SO6 control (p = 0.028).

CONCLUSION

CONCLUSION. The initial stages of experimental CKD are characterized by an increase in serum concentrations of Dikkopf-1, sclerostin and osteoprotegerin. The obtained data suggest the possible role of canonical Wnt signaling inhibition and reduction of bone turnover in the pathogenesis of Pi metabolic disorders in early stages of CKD.

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