Prenatal hypoxia (PH) is a key factor in the development of long-term cardiovascular disorders, which are caused by various mechanisms of endothelial dysfunction (ED), including those associated with NO deficiency. This emphasizes the potential of therapeutic agents with NO modulator properties, such as Thiotriazoline, Angiolin, Mildronate, and L-arginine, in the treatment of PH. Methods: Pregnant female rats were given a daily intraperitoneal dose of 50 mg/kg of sodium nitrite starting on the 16th day of pregnancy. A control group of pregnant rats received saline instead. The resulting offspring were divided into the following groups: Group 1—intact rats; Group 2—rat pups subjected to prenatal hypoxia (PH) and treated daily with physiological saline; and Groups 3 to 6—rat pups exposed to prenatal hypoxia and treated daily from the 1st to the 30th day after birth. Levels of sEPCR, Tie2 tyrosine kinase, VEGF-B, SOD1/Cu-Zn SOD, GPX4, and GPX1 in the heart’s cytosolic homogenate were assessed using ELISA. The expression of VEGF and VEGF-B mRNA was analyzed via real-time polymerase chain reaction, and the nuclear area of myocardial microvessel endothelial cells was evaluated morphometrically. Results: We have shown that only two representatives of this group—Angiolin and Thiotriazoline—are able to exert full effect on the indices of endothelial dysfunction after PH to decrease sEPCR, increase Tie-2, VEGF-B and VEGF-B mRNA, Cu/ZnSOD, and GPX in myocardial cytosol, and increase the area of endotheliocyte nuclei in 1- and 2-month-old rats in comparison with the control. Conclusions: Our results experimentally substantiate the necessity of early postnatal cardio- and endothelioprotection using NO modulators, taking into account the role of NO-dependent mechanisms in the pathogenesis of cardiovascular system disorders in neonates after PH.

The study of mitochondrial dysfunction has become increasingly pivotal in elucidating the pathophysiology of various cerebral pathologies, particularly neurodegenerative disorders. Mitochondria are essential for cellular energy metabolism, regulation of reactive oxygen species (ROS), calcium homeostasis, and the execution of apoptotic processes. Disruptions in mitochondrial function, driven by factors such as oxidative stress, excitotoxicity, and altered ion balance, lead to neuronal death and contribute to cognitive impairments in several brain diseases. Mitochondrial dysfunction can arise from genetic mutations, ischemic events, hypoxia, and other environmental factors. This article highlights the critical role of mitochondrial dysfunction in the progression of neurodegenerative diseases and discusses the need for targeted therapeutic strategies to attenuate cellular damage, restore mitochondrial function, and enhance neuroprotection.

Patients with severe aortic valve stenosis and concomitant pulmonary hypertension show a significantly reduced survival prognosis. Right heart catheterization as a preoperative diagnostic tool to determine pulmonary hypertension has been largely abandoned in recent years in favor of echocardiographic criteria. Clinically, determination of echocardiographically estimated systolic pulmonary artery pressure falls far short of invasive right heart catheterization data in terms of accuracy. The aim of the present systematic review was to highlight noninvasive possibilities for the detection of pulmonary hypertension in patients with severe aortic valve stenosis, with a special focus on cardiovascular biomarkers. A total of 525 publications regarding echocardiography, cardiovascular imaging and biomarkers related to severe aortic valve stenosis and pulmonary hypertension were analyzed in a systematic database analysis using PubMed Central®. Finally, 39 publications were included in the following review. It was shown that the current scientific data situation, especially regarding cardiovascular biomarkers as non-invasive diagnostic tools for the determination of pulmonary hypertension in severe aortic valve stenosis patients, is poor. Thus, there is a great scientific potential to combine different biomarkers (biomarker scores) in a non-invasive way to determine the presence or absence of PH.

COVID-19 leads to disruption of the blood coagulation system, to thrombosis, hypercoagulability, as a result, to an increased risk of strokes and heart attacks. During COVID-19, endothelial dysfunction develops associated with NO deficiency with decrease in the level of SH compounds. Tiazotic acid (Thiotriazoline) has immunomodulatory, anti-inflammatory, antioxidant, anti-ischemic, cardio- and endothelioprotective, antiplatelet, hepatoprotective activity. Our studies conducted at the National Research Medical Center “University Clinic of ZSMU” with the participation of 57 patients (from 30 to 65 years old) with post-COVID syndrome, who received thiotriazol with basic therapy in either tablets (200 mg each) or suppositories Dalmaxin (0.2 g each) twice a day for 30 days. Inclusion criteria for the study were a positive PCR test for COVID-19; if the PCR test was negative, then the presence of IgM COVID-19 or IgG COVID-19 (with radiologically confirmed pneumonia). The following biochemical parameters were studied: C-reactive protein - by immunoturbodimetric method; D-dimer - by enzyme immunoassay; ferritin - by immunochemiluminescent method; endothelial NO-synthase (eNOS) - by ELISA method; alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), total bilirubin; international normalized ratio (INR) and determination of platelet aggregation. During treatment with thiotriazoline, significant increase in the eNOS content was recorded, which indicated the presence of endothelioprotective activity of the drug. Thiotriazoline significantly reduced the level of D-dimer in the blood of patients, and also led to the normalization of INR. The established effects testified to the presence of antiplatelet and fibrinolytic action of thiotriazoline and its ability to reduce the risks of heart attacks and strokes in post-COVID syndrome. Thiotriazoline led to an objective improvement in general clinical parameters in patients with post-COVID syndrome, complaints of palpitations disappeared, blood pressure stabilized.

The aim was to study the influence of periodontal pocket microecology state on the local nonspecific resistance in steelworkers with generalized periodontitis. Materials and methods. In total, 178 patients were examined. The study group consisted of 126 patients with generalized periodontitis of initial (n = 8), I (n = 32), II (n = 68) and III (n = 18) degree of severity, chronic course, exposed to work-related hazardous agents. The comparison group consisted of 32 patients with periodontitis of initial (n = 5), I (n = 10), II (n = 11) and III (n = 6) degree of severity without exposure to harmful conditions of steel industry. The control group included 20 otherwise healthy individuals. Detection of the main five periodontopathogenic microorganisms in the crevicular fluid was carried out by the polymerase chain reaction method. The levels of lactoferrin and cathelicidin LL-37 were measured by the enzyme-linked immunosorbent assay method. Results. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were less common, than other opportunistic bacteria in both study groups with initial severity of generalized periodontitis. With the disease development, there was a tendency to increase the number of positive samples for all microorganisms. A correlation was found between the microorganism presence in the sample and the severity of periodontal disease. In the patients of clinical groups, the concentration of cathelicidin LL-37 in the oral fluid was reduced. In the study group, a moderate inverse correlation between cathelicidin and Porphyromonas gingivalis as well as a weak inverse correlation between cathelicidin and Prevotella intermedia were revealed. Lactoferrin was correlated directly and moderately with Porphyromonas gingivalis and Prevotella intermedia but weakly - with Treponema denticola. In the comparison group, there were a statistically significant moderate inverse correlation between cathelicidin and Porphyromonas gingivalis as well a direct correlation between lactoferrin and Porphyromonas gingivalis. Correlations between the concentrations of cathelicidin and lactoferrin in the oral fluid and other periodontopathogens were revealed to be weak. Conclusions. The studies have shown significant disruptions of the oral cavity microecology in the patients exposed to harmful effects of steel industry. The correlation between the concentration of antimicrobial peptides and periodontal pathogens in the periodontal pockets has been found.

Purpose of the article: to study the effect of acelysine and nimodipine on certain endothelial dysfunction indicators and to evaluate their therapeutic efficacy after subarachnoid hemorrhage in rats. Materials and Methods: an experimental study was carried out using 50 Wistar rats of both sexes. Spontaneous subarachnoid hemorrhage was modeled in animals. Three groups of animals were identified: a control group, a group of animals received a standard therapeutic dose of acelysine, and a group received a standard therapeutic dose of nimotop. Each group included 15 animals. There were also 5 intact animals. The animals were withdrawn from the experiment on days 4 and 7 after the motor and exploratory activity determination. Motor and exploratory activity determination was carried out following SAH with the “Open Field” technique. Determination of biochemical markers of endothelial dysfunction was performed in a rat brain homogenate. Results and discussion. It was found that modeling of subarachnoid hemorrhage (SAH) led to the oxidative stress development development and the product of oxidative modification of proteins (nitrotyrosine (Ntz) on the 4th and especially on the 7th day of the experiment) increase in the brain tissues. Starting from the 4th day, we registered a compensatory increase in the activity of NO-synthase (NOS) - by 56%, followed by a decrease in its activity on the 7th day, by more than 33% against the intact group of animals. It was registered a compensatory increase in VEGF-A in rats with SAH modeling on the 4th day of the experiment and its further decrease on the 7th day. The established pathobiochemical changes in the brain tissue were accompanied by the cognitive deficit development in experimental animals, especially on the 7th day of the SAH. SAH led to a significant decrease in the total activity of animals by 2.63 times, a decrease in the distance traveled by animals by 1.89 times, the number of freezes increased by 1.86 times and the immobility of animals increased when moving from the periphery to the center and immobility in the center of the arena (anxiety, fear, disorientation), as well as a decrease in the distance traveled and the speed of movement in illuminated center of the arena 2 and 2.6 times, respectively. Experimental therapy with acelysine 15 mg/kg led to the normalization of biochemical indicators of endothelial dysfunction: concentration of nitrotyrosine, starting from the 4th day of the experiment, increased eNOS activity and VEGF-A concentration (by 75% and 64% on 7th day). The administration of namidopine led to less pronounced effects, statistically significant changes occurred only in relation to the VEGF-A concentration. Administration of namidopine resulted in only a slight increase in VEGF-A concentration. Acelysine and nimotope significantly increased the total activity of rats on the 7th day after SAH by 76.3% and 48.8%, respectively. In animals treated with acelysine, anxiety and fear decreased. The animals were less aggressive and more empathic - long-term grooming increased 3 times. The administration of nimotop in rats survived SAH had a less pronounced positive effect on behavior. Nimotop did not effect on indicators of general activity and did not increase the total distance traveled. Animals received nimtop were inactive by the 7th day of treatment. Conclusions: Experimental therapy with acelysine led to the normalization of biochemical parameters of endothelial dysfunction, namely nitrotyrosine concentration, starting from the 4th day of the experiment and increased eNOS activity and VEGF-A concentration. It should be noted that, in contrast to the rats of the control group, under prescription of acelysine, there was an increase in the concentration of eNOS and VEGF-A both on the 4th and 7th days of the experiment. The administration of namidopine led to less pronounced effects, statistically significant changes occurred only in relation to the VEGF-A concentration. The administration of acelysin to animals after SAH had a beneficial effect on the emotional status and behavior of animals, and also led to the normalization of their general activity and orientation-exploratory activity. The mechanism of edotheliotropic effect of acelysine, in our opinion, is associated with its antioxidant effects, modulating impact on endothelial NOS, as well as its property, indirectly, to influence on increase VEGF content. Nimotope therapy had no effect on the emotional status and behavior of the animals. The use of calcium channel blockers revealed such side effects as depression, drowsiness, diplopia, and disorientation

The purpose of the given research is to study the efficiency of different inhibitors of NO-synthase in conditions of experimental cerebral ischemia by their capability to limit reactions of oxidative and nitrosative stress. In the given study a non-selective NOS inhibitor - N-nitro-L-arginine; a highly selective inhibitor of neuronal NOS - N-propyl-L-arginine and a highly selective competitive inhibitor of inducible NOS - (S)-methylurea were used. Cerebral circulation impairment was simulated by means of double-sided occlusion of common carotid arteries. It has been established that neurotoxic NO effect depends on definite enzyme of NO-synthase. Analysis of the obtained data shows a limited role of neuronal isoform in conditions of experimental impairment of blood circulation. The most relevant target for pharmacological regulation of NO-dependent mechanisms of neurodestruction is iNOS because of the fact that its activity begins to increase 12 hours after ischemia development and its action is implemented during several following days.

The aim of this work is to evaluate the complex therapeutic effect of Thiotriazolin (anticoagulant, antiplatelet, metabolitotropic, endothelioprotective activity) in patients with post-COVID syndrome in comparison with basic therapy. Materials and methods. The studies involved 30 patients aged between 30 to 60 years with post-COVID syndrome. Of these, 15 persons received basic therapy (antibiotics, anticoagulants, acetylsalicylic acid), and other 15 patients received Thiotriazolin in the form of 200 mg tablets twice a day for 30 days against the background of basic therapy. Inclusion criteria were a positive PCR test for COVID-19; if the PCR test was negative, then the patients were enrolled based on the presence of IgM COVID-19 or IgG COVID-19 (with X-ray confirmed pneumonia). The rate of lung damage is up to 45 %. The patients had the following comorbidities: diabetes mellitus in the stage of compensation, arterial hypertension, ischemic heart disease without heart failure. The results of the study were calculated using the standard statistical package Statistica for Windows 13 (StatSoft Inc., № JPZ804I382130ARCN10-J), аs well as SPSS 16.0, Microsoft Office Excel 2003. Results. The inclusion of Thiotriazolin in the complex basic therapy of post-COVID syndrome led to a significant increase in the effectiveness of basic endothelioprotective, anticoagulant and antiaggregatory therapy and contributed to the prevention of thrombus formation. The administration of Thiotriazolin led to a significant improvement in general clinical parameters in patients with post-COVID syndrome – complaints of tachycardia disappeared, blood pressure was stabilized (without additional correction with antihypertensive drugs), weakness and increased fatigue disappeared. Saturation in 14 (93.4 %) patients increased to 97–98 %. In the control group only 7 (46.7 %) of 15 patients had oxygen saturation at 97–98 % level. Conclusions. The introduction of the drug Thiotriazolin in the form of 200 mg tablets twice a day for 30 days into the complex basic therapy of post-COVID syndrome leads to a significant increase in the basic endothelioprotective, antiaggregatory and anticoagulant therapy and contributes to the prevention of thrombus formation against the background of improving the state of the myocardium and vascular endothelium.

The aim of the work is to study the Klotho protein concentration in the oral fluid of patients exposed to work-related harmful factors and to reveal correlations with the content of bone tissue and vitamin D metabolism markers. Materials and methods. The study group consisted of 126 patients with generalized periodontitis of initial (n = 8), I (n = 32), II (n = 68) and III (n = 18) degree of severity, chronic course, working in hazardous conditions of the “Dniprospetsstal” plant in Zaporizhzhia. The comparison group consisted of 32 periodontitis patients of initial (n = 5), I (n = 10), II (n = 11) and III (n = 6) degree of severity without exposure to work-related harmful factors. The control group included 20 otherwise healthy individuals aged 19–25 years without signs of periodontal diseases. The levels of vitamin D, VDBP, MMP-8 and osteocalcin were determined by enzyme-linked immunosorbent assays, the concentration of soluble Klotho was detected by the enzyme-linked ImmunoChem-2100 immunosorbent assay. Results. It was found, that in the study group of patients working in hazardous work-related conditions, the decrease in oral fluid Klotho protein concentration was greater, than in the comparison group of patients with periodontal diseases, but not exposed to work-related hazardous conditions. The indicator of Klotho protein is an early marker of the periodontal disease progression and varies inversely with the severity of periodontitis, starting in the early stages of the disease. The correlation coefficient between the level of Klotho protein and the degree of the disease severity in the comparison group patients was γ = -0.957, P < 0.05 and γ = -0.906, P < 0.05 – in the study group. In the patients with periodontal diseases, there was a decrease in the Klotho protein concentration with a parallel increase in the marker of bone tissue destruction - MMP-8, and a decrease in the marker of remodeling – osteocalcin, as compared to the controls. The decrease in Klotho protein concentration occurred with vitamin D deficiency and worsened with the vitamin D-binding protein reduction. Conclusions. The Klotho protein is the early, sensitive and specific diagnostic biomarker in dental diseases, and its measurement can be used as a predictor of inflammatory periodontal disease and its complications. The Klotho protein is one of the main regulators of bone metabolic processes.

Currently, central nervous and cardiovascular system disorders of hypoxia genesis are widely treated with drugs that restore blood flow, as well as drugs that affect cell metabolism, namely, individual units of adaptive molecular-biochemical reactions. Of particular interest are pharma-correction methods of affecting synthesis and expression of Klotho proteins, such as vitamin D and Necrostatin-1, estrogens. The purpose of the study was to identify the ability of vitamin D and tamoxifen estrogen receptor modulator to affect Klotho protein synthesis (under hypoxia in vitro modeling in brain and heart cells). The study was performed on sexually mature white non-linear rats - males weighing 190-230 g. Hypoxia in vitro was modeled by insertion of 0.6 μM concentration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridil (MPTP) into the suspension of respiratory tract tissue differentiator cardiomyocytes. By means of immunoenzyme analysis, concentration of Nitrotyrosin (Ntz) (ELISA Kit "Hycult biotechnology b.v.") and Klotho protein (Elabscience, USA) in cell suspensions was evaluated. Statistical processing of the results was carried out using the STATISTICA® for Windows 6.0 program (StatSoft Inc., No. AXXR712D833214FAN5). The reliability of the differences was carried out using the Student's t-criterion. The data analysis demonstrated that a 120-minute MPTP incubation of cardiomyocytes and neurocytes resulted in a significant deficiency of Klotho protein concentration compared to intact suspensions. Such a decrease, in our opinion, is related to the development of oxidative stress in cell suspension (increase of Ntz by 65% ​​and 69% in the cardiomyocyte and neurocyte suspensions, respectively), as well as hyperproduction of proinflammatory cytokines such as tumor necrosis factor (TNF) and interferon (INF). Vitamin D (10-7) addition to the incubation medium of cardiomyocytes and neurocytes resulted in the increase of Klotho protein content by 56% on average, with 36% and 42% reduction of Ntz concentration, respectively. The registered effects of vitamin D are explained with its direct stimulating of the expression and synthesis of Klotho protein and limiting FGF23 hyperproduction. The introduction of tamoxifen estrogen receptor modulator (10-7) into the cardio- and neurocyte incubation medium did not affect Klotho protein concentration (an increase in concentration of 34% and 28% respectively) in advanced cell suspensions as much as vitamin D, however, nitrotyrosine concentration decrease made a more expressed impact, on average by 52% and 60%. The effects of tamoxifen are implemented due to its impact on the HSP proteins system, which provides the structural and functional integrity of the Klotho protein.

Previously published data on experiences of the different quarantine measures or outbreaks in the public health system related to the SARS virus, Ebola virus, Influenza infections were analyzed in the article. The aim of the article was to identify, appraise and synthesize the best available evidences from the systematic reviews for the possible psychological impact of quarantine on the learning on health care in medical university in conditions of isolation during pandemic COVID-19 and to propose approaches to solve these problems. These findings were appraised in prism of the medical education and avaliable approaches to the e-learning of medical students. Self-experience of the Zaporizhzhia State Medical University was also included. On the background of the published results of the studies revealing the stressors some solutions for the identified problems were proposed relating to the data of the reviews. Particular attention is paid to the effect of the self e-learning on the result of the knowledge achievement. Among main stressful factors were indicated the following: fear of infection, frustrating, boredom, inability to take part in usual day-to-day activities, lack of contact with patients. Role of the teacher in reducing the burden of stress in students during quarantine was covered. Benefits and pitfalls of on-line education were assessed. The future unsolved problems were discussed.

Исследования посвящены изучению влияния цитиколина, фенилпирацетама, пентоксифиллина и N-фенилацетил-L-пролилглицина на мнестические процессы и функциональное состояние митохондрий в неокортексе крыс c аллоксановой гипергликемией. Оценку влияния препаратов на мнестические процессы проводили с помощью условной реакции пассивного избегания в темно-светлой камере. Регистрировали латентный период и число животных с амнезией навыка на 6 и 20 сут введения препаратов. Функциональное состояние митохондрий оценивали по открытию митохондриальной поры и митохондриальному трансмембранному потенциалу (Ψ) на 20 сут. Установлено, что курсовое применение фенилпирацетама, цитиколина и, в меньшей степени, N-фенилацетил-L-пролилглицина, но не пентоксифиллина, улучшало процессы обучения и хранения условного навыка. При этом ноотропная активность изученных средств была сопоставима с их влиянием на функциональное состояние митохондрий нейронов неокортекса крыс с хронической гипергликемией. Степень митопротективной активности (предупреждение открывания митохондриальной циклоспорин-А-чувствительной поры и восстановление митохондриального трансмембранного потенциала) была наибольшей у цитиколина и фенилпирацетама, а наименьшей — у пентоксифиллина.

В статье авторами исследован нейрохимический профиль нейропротективного действия селективного модулятора эстрогеновых рецепторов – тамоксифена цитрата на модели острой церебральной ишемии (ОЦИ). Показано, что моделирование ОЦИ сопровождается выраженными патобиохимическими изменениями в мозговой ткани: резкое смещение тиол-дисульфидного равновесия, интенсификация процессов свободнорадикального окисления, нарушения синтеза цитопротективных белков теплового шока Hsp 70. Курсовое введение экспериментальным животным тамоксифена цитрата в дозе 1 мг/кг, приводило к нормализации показателей тиол-дисульфидной системы, за счет повышения уровня глутатиона в мозговой ткани, что в свою очередь ограничивало развитие оксидативного и нитрозильного стрессов. Кроме того, методом иммуноблоттинга показана способность тамоксифена цитрата статистически достоверно повышать содержание Hsp 70 белков в мозговой ткани, обусловленное его геномными и внегеномными эффектами. Установленный нами нейропротективный профиль тамоксифена цитрата обусловливает дальнейшую перспективность исследований в данном направлении, с целью внедрения его в клиническую практику в качестве нейропротективного средства.

We studied the neurochemical aspects of the neuroprotective action of a selective modulator of the estrogen receptors, tamoxifen citrate, in a model of acute cerebral ischemia (ACI). It was shown that modeling of cerebral ischemia is followed by pathobiochemical changes in the brain tissue: a rapid shift of thioldisulfide homeostasis, intensification of free radical oxidation, and impaired synthesis of the cytoprotective protein Hsp70. A course of the 1 mg/kg tamoxifen citrate led to the normalization of the thiol-disulfide system due to an increase of the glutathione level in the brain tissue which, in turn, restricted the development of oxidative and nitrosative stress. In addition, Western blot analysis showed that treatment with tamoxifen citrate increased the Hsp70 level in the brain tissue, which resulted from genomic and non-genomic actions. The neuroprotective profile of tamoxifen citrate that we found here opens the future perspective of the studies in this field for introduction of this agent as a neuroprotective drug into clinical practice.

В монографии представлена современная концепция молекулярнобиохимических механизмов гибели нейронов в условиях острой церебральной ишемии.Показана роль глутамат-кальциевого каскада (изменения метаболизма глутамата и кальция, оксидативный стресс, гиперпродукция NO  ), митохондриальной дисфункции, дискоординации тиол-дисульфидной системы, которые индуцируют отдаленные последствия ишемии -реакцию генома с включением генетически запрограммированных молекулярных механизмов, дисфункцию астроцитарного и микроглиального пулов, развитие иммунных изменений и инициацию нейроапоптоза.Представлены данные о значении молекулярных факторов эндогенной нейропротекции.Выделены два основных направления терапии мозгового инсультапервичная нейропротекция, направленная на прерывание быстрых механизмов некротической смерти клеток и вторичная нейропротекция, цель которой -уменьшение выраженности отдаленных последствий ишемии (блокада провоспалительных цитокинов, молекул клеточной адгезии, торможение оксидативного стресса, нормализация нейрометаболических процессов, ингибирование апоптоза

It was established in experiments on the rats in the acute period of modeling pituitrin-isadrin myocardial infarction the formation of nitrogen monoxide decreases along with its accelerated transformation into peroxynitrite. It was evidenced by more than double inhibition of NO synthase activity in the myocardium and by decreasing the amount of nitrates on the background of the increasing level of peroxynitrites' marker--nitrotyrosine by 246.6% at an average. Experimental therapy of rats by ademol which is a derivate of adamantan (1-adamantiloxy-3-morpholino-2 propanol hydrochloride) better than by corvitin normalizes the processes of synthesis of nitric oxide. At the same time ademol probably exceeded the reference drug in ability to increase NO synthase activity and amount of nitrate, and promoted a decrease of the level of nitrotyrosine in the myocardium on the average by 36.3; 50.6 and 12.7%, respectively. Corrective influence of ademol on indicators of metabolism in NO system under the conditions of acute cardiac ischemia indicates to promicing development of domestic cardioprotector on its base.

Острая или хроническая ишемия мозговой ткани обуславливает целый каскад патобиохимических реакций, которые в конечном итоге приводят к развитию очагового неврологического дефицита, дисциркуляторной энцефалопатии или к гибели больного. В различные сроки ишемии (1 ч, 6 ч, 24 ч, 48 ч, 72 ч, 120 ч и 21 сут) установлено, что в период наибольших ишемических нарушений (24–72 ч) наблюдается гиперпродукция лактата на фоне угнетения гексокиназы (ГК) – фермента, катализирующего первую “пусковую” реакцию гликолиза. Рост малата с повышением активности митохондриальной (мМДГ) и цитозольной (цМДГ) малатдегидрогеназ в первые часы церебральной ишемии свидетельствует об активации малат-аспартатного челночного механизма транспорта восстановленных эквивалентов в митохондрии. Угнетение продукции малата и активности НАД-зависимой малатдегидрогеназы (НАД-МДГ-мх) коррелирует с падением АТФ, HSP-70 и фактора, индуцируемого гипоксией (HIF-1a), а также со степенью неврологических нарушений. Можно предположить, что в ответ на формирование ишемии головного мозга экспрессируется HIF-1a, который инициирует запуск компенсаторных механизмов выработки энергии. В дальнейшем регуляция этих процессов переключается на HSP-70, который “пролонгирует” действие HIF-1a, а также самостоятельно поддерживает экспрессию активности НАД-МДГ-мх, тем самым длительно поддерживая активность малат-аспартатного челночного механизма.