zdorПроблемы здоровья и экологииHealth and Ecology Issues2220-09672708-6011Gomel State Medical University10.51523/2708-6011.2024-21-2-11zdor-2717Research ArticleЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНА И БИОЛОГИЯEXPERIMENTAL MEDICINE AND BIOLOGYКорреляционные взаимосвязи между уровнем микроРНК и мРНК вовлекаемых в патологический ангиогенез в условиях экспериментального цирроза печениCorrelation relationships between the levels of microRNA and mRNA involved in pathological angiogenesis in experimental liver cirrhosishttps://orcid.org/0000-0003-1309-4248ЛебедеваЕ. И.LebedevaE. I.

Лебедева Елена Ивановна, к.б.н., доцент, доцент кафедры гистологии, цитологии и эмбриологии,

г. Витебск

Elena I. Lebedeva, Candidate of Biological Sciences, Associate Professor at the Department of Histology, Cytology and Embryology

Vitebsk

lebedeva.ya-elenale2013@yandex.ruhttps://orcid.org/0000-0003-2796-4240ЩастныйА. Т.ShchastniyA. T.

Щастный Анатолий Тадеушевич, д.м.н., профессор, заведующий кафедрой госпитальной хирургии с курсомФПКиПК

г. Витебск

Anatoliy T. Shchastniy, Doctor of Medical Sciences, Professor, Head of the Department of Hospital Surgery with the course of Advanced Training and Retraining

Vitebsk 

rectorvsmu@gmail.comhttps://orcid.org/0000-0002-5513-970XБабенкоА. С.BabenkaA. S.

Бабенко Андрей Сергеевич, к.х.н., доцент, доцент кафедры общей химии

г. Минск

Andrei S. Babenka, Candidate of Chemical Sciences, Associate Professor at the Department of General Chemistry

Мinsk

labmdbt@gmail.comhttps://orcid.org/0000-0002-3808-8832ЗиновкинД. А.ZinovkinD. A.

Зиновкин Дмитрий Александрович, к.б.н., доцент, доцент кафедры патологической анатомии

г. Гомель

Dmitry A. Zinovkin, Candidate of Biological Sciences, Associate Professor, Associate Professor at the Department of Pathology

Gomel

zinovkin_da@gsmu.byhttps://orcid.org/0000-0002-0896-5611НадыровЭ. А.NadyrovE. A.

Надыров Эльдар Аркадьевич, к.м.н., доцент, доцент кафедры патологической анатомии

г. Гомель

Eldar A. Nadyrov, Candidate of Medical Sciences, Associate Professor, Associate Professor at the Departments of Pathological Anatomy and Histology, Cytology and Embryology

Gomel

nadyrov2006@rambler.ruВитебский государственный ордена Дружбы народов медицинский университетVitebsk State Order of Peoples’ Friendship Medical UniversityБелорусский государственный медицинский университет.Belarusian State Medical UniversityГомельский государственный медицинский университетGomel State Medical University2024270520242128796Copyright © Лебедева Е.И., Щастный А.Т., Бабенко А.С., Зиновкин Д.А., Надыров Э.А., 20242024Лебедева Е.И., Щастный А.Т., Бабенко А.С., Зиновкин Д.А., Надыров Э.А.Lebedeva E.I., Shchastniy A.T., Babenka A.S., Zinovkin D.A., Nadyrov E.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.gsmu.by/jour/article/view/2717Цель исследования

Цель исследования. Выявить взаимосвязи между уровнем микроРНК и мРНК при патологическом ангиогенезе в условиях экспериментального токсического цирроза печени.

Материалы и методы

Материалы и методы. Фиброз и цирроз печени у крыс-самцов линии Wistar индуцировали свежеприготовленным раствором тиоацетамида в течение 17 недель. Динамику процесса изучали в девяти временных точках. Измеряли площадь междольковых вен и междольковых артерий в микрометрах. Подсчитывали количество междольковых артерий, междольковых вен и синусоидных капилляров. Уровень экспрессии мРНК генов Ang, Vegfa, Tweak, Fn14, Notch1, Notch2 и микроРНК-195-5р, микроРНК-664-3р, микроРНК-489-3р, микроРНК-3085, микроРНК-3558-3р в печени определяли методом полимеразной цепной реакции в режиме реального времени.

Результаты

Результаты. Установлено, что при прогрессирующем венозном ангиогенезе, а также на фоне изменения количества междольковых вен, синусоидных капилляров, площади междольковых вен характер и сила корреляционных взаимодействий между генами Ang, Vegfa, Tweak, Fn14, Notch1, Notch2 и микроРНК-195-5р, микроРНК-664-3р, микроРНК-489-3р, микроРНК-3085, микроРНК-3558-3р связаны со стадией фиброза и цирроза печени. Выявлены прямые сильные, средние и умеренные корреляционные связи (p < 0,01) между генами Ang, Vegfa, Tweak, Fn14, Notch1, Notch2 на протяжении всего эксперимента.

Заключение

Заключение. Полученные результаты свидетельствуют о том, что исследуемые нами микроРНК-195-5р, микроРНК-664-3р, микроРНК-489-3р, микроРНК-3085, микроРНК-3558-3р вовлекаются в процессы перестройки внутрипеченочного сосудистого русла на разных стадиях экспериментального токсического фиброза и цирроза печени. Результаты исследования позволяют не только раскрыть дополнительные механизмы формирования указанных состояний, но и выявить биологическую роль изученных микроРНК в прогрессировании фиброза и цирроза печени в качестве потенциальных мишеней для изучения патогенеза и разработки методов лечения.

Objective

Objective. To identify the relationships between the levels of microRNA and mRNA during pathological angiogenesis under the conditions of experimental toxic liver cirrhosis.

Materials and methods

Materials and methods. Fibrosis and liver cirrhosis were induced in male Wistar rats using a freshly prepared solution of thioacetamide over 17 weeks. The dynamics of the process were studied at 9 time points. The areas of interlobular veins and interlobular arteries were measured in micrometers. The numbers of interlobular arteries, interlobular veins, and sinusoidal capillaries were counted. The expression levels of mRNA genes Ang, Vegfa, Tweak, Fn14, Notch1, Notch2, and microRNAs-195-5p, microRNAs-664-3p, microRNAs-489-3p, microRNAs-3085, microRNAs-3558-3p in the liver were determined by real-time polymerase chain reaction.

Results

Results. It was found that during progressive venous angiogenesis, as well as against the background of changes in the number of interlobular veins, sinusoidal capillaries, and the area of interlobular veins, the nature and strength of correlational interactions between the genes Ang, Vegfa, Tweak, Fn14, Notch1, Notch2, and microRNAs-195-5p, microRNAs-664-3p, microRNAs-489-3p, microRNAs-3085, microRNAs-3558-3p are associated with the stage of fibrosis and liver cirrhosis. Strong, moderate, and mild correlational links (p<0.01) were identified between the genes Ang, Vegfa, Tweak, Fn14, Notch1, Notch2 throughout the experiment.

Conclusion

Conclusion. The obtained results indicate that the studied microRNAs - microRNAs-195-5p, microRNAs-664-3p, microRNAs-489-3p, microRNAs-3085, microRNAs-3558-3p - are involved in the processes of restructuring the intrahepatic vascular bed at different stages of experimental toxic fibrosis and liver cirrhosis. The results of the study not only reveal additional mechanisms of formation of the indicated conditions but also identify the biological role of the studied microRNAs in the progression of fibrosis and liver cirrhosis as potential targets for studying pathogenesis and developing treatment methods.

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