microcirculationРегионарное кровообращение и микроциркуляцияRegional blood circulation and microcirculation1682-66552712-9756Academician I.P. Pavlov First St. Petersburg State Medical University10.24884/1682-6655-2022-21-3-82-90microcirculation-1105Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ (ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ)ORIGINAL ARTICLES (EXPERIMENTAL INVESTIGATIONS)Оценка антиоксидантного действия различных ангиопротективных препаратов по степени дегрануляции тучных клеток при фотодинамическом поврежденииAntioxidant effect evaluation of drugs with different chemical structures by the degree of mast cell degranulation under photodynamic damageСонинД. Л.SoninD. L.

Сонин Дмитрий Леонидович – канд. мед. наук, ведущий научный сотрудник, зав. Научно-исследовательским отделом микроциркуляции и метаболизма миокарда

197341, Санкт-Петербург, ул. Аккуратова, д.

197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8

Sonin Dmitry L. – Cand. of Sci. (Med.), Head of the Department of microcirculation and cardiac metabolism

2, Akkuratova str., Saint Petersburg, 1973416-8, L’va Tolstogo str., Saint Petersburg, 197022

 

lasmed@yandex.ruФайзуллинаД. Р.FayzullinaD. R.

Файзуллина Динара Рафаэлевна – ассистент афедры патофизиологии с курсом клинической патофизиологии

197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8

Faizullina Dinara R. – assistant of the Department of Pathophysiology with a course of Clinical Pathophysiology

6-8, L’va Tolstogo str., Saint Petersburg, 197022

ЗайцеваЕ. А.ZaitsevaE. A.

Екатерина Андреевна Зайцева – младший научный сотрудник Научно-исследовательского отдела микроциркуляции и метаболизма миокарда

197341, Санкт-Петербург, ул. Аккуратова, д. 2

Zajtseva Ekaterina A. – Junior Research Fellow of the Department of microcirculation and cardiac metabolism

2, Akkuratova str., Saint Petersburg, 197341

ПетрищевН. Н.PetrishchevN. N.

Петрищев Николай Николаевич – д-р мед. наук, профессор кафедры патофизиологии с курсом клинической патофизиологии, руководитель центра лазерной медицины Научно-образовательного института биомедицины

197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8

Petrishchev Nikolay N. – Doctor of Medical Sciences, Professor of the Department pathophysiology with a course of clinical pathophysiology, Head of the Center for Laser Medicine of Scientific and Educational Institute of Biomedicine

6-8, L’va Tolstogo str., Saint Petersburg, 197022

Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр имени В. А. Алмазова» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияAlmazov National Medical Research Centre; Pavlov UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияPavlov UniversityRussian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр имени В. А. Алмазова» Министерства здравоохранения Российской ФедерацииРоссияAlmazov National Medical Research CentreRussian Federation2022121020222138290Copyright © Сонин Д.Л., Файзуллина Д.Р., Зайцева Е.А., Петрищев Н.Н., 20222022Сонин Д.Л., Файзуллина Д.Р., Зайцева Е.А., Петрищев Н.Н.Sonin D.L., Fayzullina D.R., Zaitseva E.A., Petrishchev N.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.microcirc.ru/jour/article/view/1105

Введение. На модели острого воспаления кожи, вызванного фотодинамическим повреждением (ФП), в котором ведущая роль принадлежит активным формам кислорода (АФК), изучены нарушения микроциркуляции (МКЦ) и дегрануляция ТК (ТК) в месте воздействия. Научный интерес представляет изучение IgE-независимых механизмов активации ТК и возможность их фармакологической коррекции. Цель – оценить возможности использования модели острого воспаления, индуцированного АФК, при ФП для изучения вклада ТК в регуляцию проницаемости сосудов и изучения ангиопротекторных и улучшающих МКЦ препаратов на доклиническом этапе. Материалы и методы. Крысам-самцам стока Wistar вводили фотосенсибилизатор, через 3 ч наркотизировали и проводили облучение лазером, затем вводили один из следующих препаратов: гидрокортизон (ГК), этилметилгидроксипиридина сукцинат (ЭС) или квинакрин (КК). Оценку МКЦ кожи проводили методом лазерной допплеровской флуометрии. Подсчет и морфометрию ТК производили в пленочных препаратах рыхлой соединительной ткани кожи. Результаты. Сразу после ФП кровотока показатель микроциркуляции в контрольной группе составил 1,9 [1,4;2,3] п. е., что на 55 % меньше исходного. Через час наблюдалось частичное восстановление кровотока до 3,7 [3,3;4,0] п. е. (88 % от исходного, p<0,001). Несмотря на введение ГК и ЭС, кровоток после ФП снижался на 8,5 и 32,5 % соответственно и через час составлял только 78 % от исходного. После введения КК сразу после облучения снижение составило только 28 %, через час кровоток полностью восстанавливался. Степень дегрануляции ТК после введения ГК и КК сопоставима и сопровождается снижением количества ТК с полной (анафилактической) дегрануляцией до 27,5 [21,6; 29,4] и 26,4 [22,5; 32,5] % соответственно, против 46,9 [47,7; 52] % в контрольной группе (р<0,05); однако после введения ЭС результаты сопоставимы с интактным контролем. При проведении непараметрического корреляционного анализа не были выявлены статистически значимые взаимосвязи тканевой перфузии через час после фотодинамического воздействия и морфометрическими типами ТК с использованием различных препаратов. Заключение. Разнонаправленность влияния препаратов на перфузию и структуру популяции ТК подтверждается отсутствием выявленной корреляции между данными параметрами. КК, в сравнении с ЭС и ГК, более эффективен в отношении нарушений МКЦ. В этих условиях перспективным представляется сочетанное использование противовоспалительных и антиоксидантных препаратов.

Introduction. This model of skin acute inflammation caused by photodynamic damage (PHD), where reactive oxygen species (ROS) play a key role, enables the analysis of the microcirculation (MCC) dysfunction and degranulation of mast cells (MCs) at the site of exposure. The current study explored the IgE-independent mechanisms of MCs activation caused by PHD and the possibility of its pharmacological correction. Aim of the study – to evaluate the possibilities of using the model of acute inflammation induced by ROS during PHD to study the MCs contribution to the regulation of vascular permeability and to study angioprotective and MCC-improving drugs at the preclinical stage. Materials and methods. Male Wistar rats were injected with a photosensitizer, then anesthetized and laser irradiated 3 hours later, followed by one of the following drugs: hydrocortisone (HC), ethylmethylhydroxypyridine succinate (ES), or quinacrine (QC). Skin MCC was investigated by laser Doppler flowmetry. Calculation and morphometry of MCs was carried out on film preparations of loose connective tissue of the skin. Results. Immediately after PHD, the blood flow in the control group was 1.9 [1.4; 2.3] p. u., which is 55 % less than the initial values. Partial restoration of blood flow up to 3.7 [3.3; 4.0] p.u. was observed after one hour of observation (88 % of baseline, p<0.001). Despite the administration of HC and ES, the blood flow after PHD decreased by 8,5 and 32,5 %, respectively. After an hour, it was only 78 % of the baseline. Intravenous administration of QC immediately after irradiation, lead to decrease of the blood flow only 28 %, and after an hour the blood flow was completely restored. The degree of MCs degranulation after the intravenous administration of HC and QC is almost equal and characterized by a decrease in the number of MCs with complete (anaphylactic) degranulation to 27.5 [21.6; 29.4] and 26.4 [22.5; 32.5] %, respectively, versus 46.9 [47.7; 52] % in the control group (p<0,05); however, after the administration of ES, the results are comparable with the intact control. Non-parametric correlation analysis did not reveale statistically significant difference between blood flow one hour after photodynamic exposure and morphometric types of MCs in groups with various drugs. Conclusion. Differences between the drug effects on the skin blood flow and the IgE-independent MCs activation is confirmed by the absence of a correlation between these parameters. QC, in comparison with ES and HC, is more effective in relation to dysfunction of the skin MCC. Under these conditions, the combined use of anti-inflammatory and antioxidant drugs seems promising.

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