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DOI 10.34014/2227-1848-2022-2-102-116

ALCOHOL-INDUCED EXPRESSION OF VASCULAR ENDOTHELIALGROWTH FACTOR AND STRUCTURAL CHANGES IN RAT CARDIOMYOCYTES

P.V. Belogubov, V.I. Ruzov, S.M. Clesarev, R.R. Sharafutdinova

Ulyanovsk State University, Ulyanovsk, Russia

 

The aim of the study is to reveal the ethanol effects on the expression of hypoxia-associated factors (HIF-1α, VEGF-A) and structural changes in cardiomyocytes of healthy rats.

Materials and methods. Ethanol-induced structural changes in cardiomyocytes were studied in 60 outbred mature rats. Control animals were intragastrically injected with sterile 0.9% saline, experimental animals – with 40 % ethanol. Ethanol exposure on myocardium lasted 4 and 8 days. Morphological study of the heart was carried out after decapitation preceded by ether anesthesia. PCR tests were used to determine mRNA expression of HIF-1α and VEGF-A genes from the left ventricle and serum concentration of vascular endothelial growth factor. Morphological studies of the left ventricle myocardium were carried out on histological sections using light microscopy.

Results. A short ethanol exposure was accompanied by fatty and granular cytoplasm degeneration of cardiomyocytes with erythrocyte stasis in capillaries, arterioles and venules. VEGF-A serum concentration in control rats was lower if compared with ethanol-induced rats. Gender differences to ethanol response were revealed, in particular, a more pronounced HIF-1α and VEGF-A mRNA expression in females compared to males on the background of 4-day ethanol exposure, which correlated with VEGF-A level in blood serum. 8-day alcohol exposure was accompanied by an increase in VEGF-A mRNA expression in both female and male rats.

Conclusion. Ethanol exposure causes activation of HIF-1α and VEGF-A transcription factors in cardiomyocytes of rats. It can be regarded as a mechanism of urgent adaptation without the development of pronounced structural maladaptive changes of the myocardium.

Key words: VEGF-A, HIF-1α, hypoxia-associated factors, ethanol exposure, mRNA expression, alcohol-induced myocardial changes.

 

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 Received 12 March 2022; accepted 13 May 2022.

 

Information about the authors

Belogubov Pavel Vasil'evich, Post-graduate Student, Chair of Faculty Therapy, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-8377-1569

Ruzov Viktor Ivanovich, Doctor of Sciences (Medicine), Professor, Honored Doctor of the Russian Federation, Head of the Chair of Faculty Therapy, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0001-7510-3504

Slesarev Sergey Mikhaylovich, Doctor of Sciences (Biology), Associate Professor, Head of the Chair of Biology, Ecology and Nature Management, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-5080-1004

Sharafutdinova Rizida Rafaelevna, Post-graduate Student, Chair of Faculty Therapy, Teaching Assistant, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-2768-5452

 

For citation

Belogubov P.V., Ruzov V.I., Clesarev S.M., Sharafutdinova R.R. Indutsirovannaya alkogolem ekspressiya sosudistogo endotelial'nogo faktora rosta i strukturnye izmeneniya kardiomiotsitov krys [Alcohol-induced expression of vascular endothelial growth factor and structural changes in rat cardiomyocytes]. Ul'yanovskiy mediko-biologicheskiy zhurnal. 2022; 2: 102–116. DOI: 10.34014/2227-1848-2022-2-102-116 (in Russian).

 

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УДК 616-092.9

DOI 10.34014/2227-1848-2022-2-102-116

ИНДУЦИРОВАННАЯ АЛКОГОЛЕМ ЭКСПРЕССИЯ СОСУДИСТОГО ЭНДОТЕЛИАЛЬНОГО ФАКТОРА РОСТА И СТРУКТУРНЫЕ ИЗМЕНЕНИЯ КАРДИОМИОЦИТОВ КРЫС

П.В. Белогубов, В.И. Рузов, С.М. Cлесарев, Р.Р. Шарафутдинова

ФГБОУ ВО «Ульяновский государственный университет», г. Ульяновск, Россия

 

Цель – выявить влияние этанола на экспрессию связанных с гипоксией генов (HIF-1α, VEGF-А) и структурные изменения в кардиомиоцитах здоровых крыс.

Материалы и методы. Структурные изменения кардиомиоцитов под воздействием этанола изучались на 60 беспородных половозрелых крысах. Животным контрольной группы вводился интрагастрально стерильный 0,9 % водный раствор хлорида натрия, остальным животным – 40 % этанол. Длительность воздействия этанола на миокард составляла 4 и 8 сут. Морфологическое исследование сердца животных проводилось после декапитации под эфирным наркозом. Определялась экспрессия мРНК генов HIF-1α и VEGF-A из участка левого желудочка сердца и сывороточная концентрация сосудисто-эндотелиального фактора роста методом ПЦР. Морфологические исследования миокарда левого желудочка сердца проводились по гистологическим срезам методом световой микроскопии.

Результаты. Короткое по продолжительности воздействие этанола сопровождалось признаками жировой и зернистой дистрофии цитоплазмы кардиомиоцитов с явлениями стаза эритроцитов в капиллярах, артериолах и венулах. Сывороточная концентрация VEGF-A у крыс контрольной группы была ниже по сравнению с группой крыс, подвергнутых воздействию этанола. Выявлены гендерные различия реакции на этанол, в частности более выраженная экспрессия мРНК HIF-1α и VEGF-A у самок по сравнению с самцами на фоне 4-дневного воздействия этанолом, что коррелировало с содержанием VEGF-А в сыворотке крови. Увеличение длительности алкогольного воздействия до 8 сут сопровождалось ростом экспрессии мРНК VEGF-A как у самок, так и самцов крыс.

Выводы. Воздействие этанола вызывает активацию транскрипционных факторов HIF-1α и VEGF-А кардиомиоцитов крыс, что может быть расценено как механизм срочной адаптации без развития выраженных структурных дезадаптационных перестроек миокарда.

Ключевые слова: VEGF-A, HIF-1α, гипоксия-ассоциированные факторы, воздействие этанола, экспрессия мРНК, алкоголь-индуцированные изменения миокарда.

 

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 Поступила в редакцию 12.03.2022; принята 13.05.2022.

 

Авторский коллектив

Белогубов Павел Васильевич – аспирант кафедры факультетской терапии, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-8377-1569

Рузов Виктор Иванович – доктор медицинских наук, профессор, заслуженный врач РФ, заведующий кафедрой факультетской терапии, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0001-7510-3504

Слесарев Сергей Михайлович – доктор биологических наук, доцент, заведующий кафедрой биологии, экологии и природопользования, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-5080-1004

Шарафутдинова Ризида Рафаэлевна – аспирант кафедры факультетской терапии, ассистент кафедры, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-2768-5452

 

Образец цитирования

Белогубов П.В., Рузов В.И., Cлесарев С.М., Шарафутдинова Р.Р. Индуцированная алкоголем экспрессия сосудистого эндотелиального фактора роста и структурные изменения кардиомиоцитов крыс. Ульяновский медико-биологический журнал. 2022; 2: 102–116. DOI: 10.34014/2227-1848-2022-2-102-116.