РЕЗЮМЕЦель. Разработать экспериментальную модель метаболического синдрома (МС) у крыс на основе высокожировой и высокоуглеводной диеты. Материалы и методы.Исследование выполнено на 20 самцах крыс линии Вистар, которые были распределены на контрольную и опытную группы. Крысы контрольной группы находились на стандартной диете. Крысы опытной группы в течение 12 нед получали высокожировую и высокоуглеводную диету, содержащую животный жир (17%), фруктозу (17%) и 20%-й раствор фруктозы вместо питьевой воды. В конце исследования у животных измеряли массу тела, артериальное давление (АД), проводили глюкозотолерантный (ГТТ) и инсулинотолерантный (ИТТ) тесты. В плазме крови определяли отдельные показатели липидного обмена, в печени -содержание триацилглицеролов (ТАГ) и холестерина (ХС).Результаты. Содержание животных на высокожировой и высокоуглеводной диете в течение 12 нед приводило к повышению АД, увеличению удельной массы висцеральной жировой ткани. Выполнение ГТТ и ИТТ позволило выявить у крыс с МС гипергликемию, нарушение толерантности к глюкозе и инсулинорезистентность. Было обнаружено увеличение концентрации ТАГ в плазме крови крыс опытной группы, при этом уровень общего ХС не отличался от контроля. У крыс с МС наблюдалось увеличение удельной массы печени, а также содержания в ней ТАГ и ХС.Заключение. Полученная экспериментальная модель диет-индуцированного метаболического синдрома воспроизводит большинство типичных признаков МС у человека и может быть полезна в изучении патофизиологических основ развития МС и методов его профилактики и лечения. Ключевые слова: метаболический синдром, высокожировая и высокоуглеводная диета, ожирение, дислипидемия, гипергликемия, инсулинорезистентность. Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи. Источник финансирования. Исследование выполнено при финансовой поддержке РФФИ и Томской области в рамках научного проекта № 19-415-703015 (№ 18-44-700009, 18-44703008) и Совета по грантам президента Российской Федерации (МК-143.2020.4). Соответствие принципам этики. Исследование выполнено с соблюдением принципов гуманности, изложенных в директивах Европейского сообщества (86/609/ЕЕС) и Хельсинкской декларации. Исследование одобрено локальным этическим комитетом СибГМУ (протокол № 7793 от 27.05.2019).

Изучена специфическая активность антиагрегантного средства индолинонового ряда (GRS) на модели АДФ-индуцированной агрегации тромбоцитов in vitro и in vivo и на модели стрептозотоцин-индуцированного сахарного диабета у крыс. В качестве препарата сравнения использована (АСК) и дипиридамол. У GRS в опыте in vitro в широком диапазоне концентраций (0,75 · 10–6 – 1,5 · 10–5 М, p < 0,05) отмечается антиагрегантная активность, сопоставимая с таковой у ацетилсалициловой кислоты и дипиридамола. В опытах in vivo показана дозозависимая антиагрегантная активность GRS в дозах 2,5 – 20 мг/кг (21 – 14 %). Увеличение дозы GRS выше 10 мг/кг не приводит к увеличению антиагрегантной активности. При курсовом внутрижелудочном введении в дозе 10 мг/кг GRS обладал антиагрегантной активностью у крыс со стрептозотоцин-индуцированным сахарным диабетом, что проявлялось снижением амплитуды агрегации тромбоцитов до значений в интактной группе (p < 0,05).

Due to high variability and rapid life cycle, influenza virus is able to develop drug resistance against direct‐acting antivirals. Development of novel virus‐in113039hibiting drugs is therefore important goal. Previously, we identified camphor derivative, camphecene, as an effective anti‐influenza compound. In the present study, we optimize the regimen of its application to avoid high sub‐toxic concentrations. The protective activity of camphecene was assessed on the model of lethal pneumonia of mice caused by influenza viruses. Camphecene was administered either once a day or four times a day, alone or in combination with Tamiflu. Mortality and viral titer in the lungs were studied. Pharmacokinetics of camphecene was studied in rabbits. We have demonstrated that camphecene, being used every 6 h at a dose of 7.5 mg/kg/day, results in antiviral effect that was statistically equal to the effect of 100 mg/kg/day once a day, that is, the same effect was achieved by 13 times lower daily dose of the drug. This effect was manifested in decrease of mortality and decrease of virus' titer in the lungs. The studies of pharmacokinetics of camphecene have demonstrated that it does not accumulate in blood plasma and that its m ultiple applications with dosage interval of 65 min are safe. In addition, the results of the study demonstrate also that camphecene possesses additive effect with Tamiflu, allowing to decrease the dose of the latter. The results suggest that due to safety and efficacy, camphecene can be further developed as potential anti‐influenza remedy.

Aim. To identify early morphological changes in the heart and aorta of rats with experimental metabolic syndrome induced by a high-fat and high-carbohydrate diet (HFHCD).Materials and methods. The study was carried out on male Wistar rats. The animals were divided into two groups: a control group (n = 10) and an experimental group (n = 10). The rats from the control group were fed with a standard laboratory diet. The rats from the experimental group received HFHCD for 12 weeks. Body weight, blood pressure (BP), and individual parameters of carbohydrate and lipid metabolism were assessed in the rats.   A histologic examination of the heart and aorta in the animals was performed.Results. Feeding rats with HFHCD led to an increase in body weight, elevation of BP, obesity, hyperglycemia, and triglyceridemia. The histologic examination of the heart in the rats of the experimental group showed signs of vascular disease, lipomatosis, and focal myocardial degeneration. Lipid accumulation in the cells of the media, hyperplasia of adipocytes in the adventitia, and depletion and fragmentation of the elastic lamina were revealed in the aortic wall of the rats receiving HFHCD.Conclusion. The study indicated that HFHCD is an effective way to model metabolic syndrome. Structural disorders in the heart and aorta may be the mainstay for the development of cardiomyopathy and arterial hypertension in diet-induced metabolic syndrome.

Introduction. The article presents the results of studying the antithrombotic activity of a novel drug, a soluble guanylate cyclase stimulator (codename -GRS), in experimental models of arterial and venous thrombosis and thromboembolism. Aim. Study the antithrombotic action of GRS compound in comparison with clopidogrel and rivaroxaban in the following models: arterial thrombosis induced by iron chloride application to carotid artery wall in rats; thromboembolism induced by intravenous administration of thrombin solution in mice; venous thrombosis induced by the ligature of inferior vena cava in rats. Materials and methods. Arterial thrombosis was modelled in rats by applying a pad soaked in iron chloride (FeCl 3 ) to the carotid artery, GRS compound was administered orally in median effective dose of 10 mg/kg once 3 hours before pad application. Blood flow in carotid arteries and blood clot mass were registered. Thromboembolism was induced in mice by intravenous administration of thrombin solution, GRS in dose 10 mg/kg or the reference drug clopidogrel were administered once orally daily for 3 days. Animal mortality, survival time and blood clot size were registered. Venous thrombosis was induced in rats by the ligature of inferior vena cava below renal veins, GRS in dose 10 mg/kg, reference drug rivaroxaban in 5 mg/kg dose or their combination in these doses were administered once orally 1 hour before vein ligature. The mass of dry and wet blood clots was registered. Results and discussion. In arterial thrombosis model GRS compound in 10 mg/kg, administered 3 hours before iron chloride application, increased the time to blood flow cessation in the carotid artery by 35 % and reduced the frequency of complete artery occlusion by 2 times compared to the control group (р < 0.05). 60 min after arterial thrombosis modelling complete occlusion was observed in 28 % of animals in GRS group and in 75 % of control animals, while after 24 hours the occlusion was observed in 14 % of animals in GRS group and in 50 % of control group animals (p < 0.05). In thrombin-induced thromboembolism model in mice GRS did not reduce the size of blood clots in pulmonary vessels, while clopidogrel reduced it by 48 %. In GRS group 80 % of animals died of thrombosis, compared to 30 % in clopidogrel group and 90 % in the control group. In ligature-induced venous thrombosis in rats GRS after single oral administration reduced the mass of dry blood clot, being as potent as rivaroxaban. Combined administration of GRS and rivaroxaban did not enhance their antithrombotic action. Conclusion. GRS after single oral administration in 10 mg/kg dose had potent antithrombotic action in models of arterial and venous thrombosis in rats, while not preventing pulmonary vessel thrombosis in mice after thrombin administration. Therapeutic action of GRS in experimental venous thrombosis was as potent as that of rivaroxaban. Antithrombotic action of GRS compound results not only from its antiplatelet action, but also from the alleviation of endothelial dysfuncti...