Журнал «Медицина неотложных состояний» Том 21, №7, 2025

Актуальність. Гострий панкреатит (ГП) є тяжкою абдомінальною патологією з високою частотою ускладнень і летальності. Одним із ключових патогенетичних механізмів цього захворювання визнано мітохондріальну дисфункцію, яка сприяє розвитку апоптозу, некрозу та системної запальної відповіді. Розробка терапевтичних підходів, спрямованих на збереження мітохондріального гомеостазу, набуває особливого значення. Матеріали та методи. Проведено систематизований аналіз експериментальних досліджень з баз PubMed, Scopus та Google Scholar, які вивчали вплив фармакологічних та біологічних агентів на мітохондріальну функцію при ГП in vivo та in vitro. Основна увага приділялась модуляції мітодинаміки, мітофагії, біогенезу, інгібуванню NLRP3-інфламасоми, а також застосуванню стовбурових клітин і нанотерапії. Результати. Результати аналізу експериментальних досліджень підтверджують, що відновлення мітохондріального гомеостазу може бути досягнуто шляхом модуляції кількох ключових процесів. Препарати з антиоксидантною активністю (мелатонін, ресвератрол, агомелатин) демонструють здатність знижувати продукування активних форм кисню, пригнічувати апоптоз ацинарних клітин і поліпшувати мембранний потенціал мітохондрій (m). Активація захисної автофагії та мітофагії шляхом застосування рапаміцину, трегалози, уролітину А, спермідину та селену сприяє елімінації дисфункціональних мітохондрій і зменшує запалення. Засоби, що стимулюють AMPK/SIRT1/PGC-1-опосередкований біогенез (метформін, AICAR, берберин, пінокембрин, німболід), відновлюють енергетичний баланс, активують антиоксидантні шляхи (Nrf2/HO-1), пригнічують каспази та інфламасому NLRP3. Інгібітори NLRP3 (MCC950, INF-39, полідатин, пеонол) значно зменшують вивільнення прозапальних цитокінів, активацію каспази-1 і піроптоз. Крім того, мезенхімальні стовбурові клітини та їхні екзосоми забезпечують передачу функціональних мітохондрій, інгібують піроптоз та знижують ураження віддалених органів. Нанотерапевтичні платформи (на основі кемпферолу, пентоксифіліну, поліфенолів, нанозимів, наночастинок ітрію, церію, іридію) забезпечують прицільну доставку в зону ушкодження, знижують оксидативний стрес, стимулюють мітофагію, зберігають m і підвищують синтез аденозинтрифосфату. Комплексне використання таких підходів дозволяє впливати на ключові ланки патогенезу ГП, зменшити тяжкість перебігу захворювання та поліпшити прогностичні показники в експериментальних моделях. Висновки. Фармакологічна модуляція мітохондріального гомеостазу відкриває нові можливості для патогенетично обґрунтованого лікування ГП. Мітохондріально-спрямована терапія є перспективним напрямом, що дозволяє зменшити пошкодження ацинарних клітин та обмежити тяжкість системних ускладнень.

Background. Acute pancreatitis is a severe abdominal condition with a high rate of complications and mortality. Mitochondrial dysfunction has been identified as a central mechanism contributing to acinar cell apoptosis, necrosis, and systemic inflammatory response. Therapeutic strategies targeting mitochondrial homeostasis are of growing importance. Materials and methods. A systematic review of experimental studies from PubMed, Scopus, and Google Scholar was performed. The focus was on the impact of pharmacological and biological agents on mitochondrial function in the in vivo and in vitro models of acute pancreatitis. Key topics included modulation of mitochondrial dynamics, mitophagy, mitochondrial biogenesis, NLRP3 inflammasome inhibition, and the use of stem cells and nanotherapy. Results. Analysis of experimental studies confirms that mitochondrial homeostasis in acute pancreatitis can be restored through the modulation of several key pathways. Antioxidant compounds such as melatonin, resveratrol, and agomelatine reduce reactive oxygen species, inhibit acinar cell apoptosis, and stabilize mitochondrial membrane potential (m). Pharmacological activation of protective autophagy and mitophagy with agents like rapamycin, trehalose, urolithin A, spermidine, and selenium promotes the clearance of dysfunctional mitochondria and attenuates inflammation. Agents that stimulate AMPK/SIRT1/PGC-1-mediated mitochondrial biogenesis (e.g., metformin, AICAR, berberine, pinocembrin, nimbolide) restore energy metabolism, activate antioxidant defense (Nrf2/HO-1), and suppress caspase and NLRP3 inflammasome activation. NLRP3 inhibitors (MCC950, INF-39, polydatin, paeonol) significantly reduce proinflammatory cytokine release, caspase-1 activation, and pyroptosis. Additionally, mesenchymal stem cells and their extracellular vesicles transfer functional mitochondria, inhibit pyroptosis, and protect distant organs. Nanotherapeutic platforms — based on kaempferol, pentoxifylline, polyphenols, nanozymes, yttrium, cerium, and iridium nanoparticles — enable targeted delivery to injured tissues, decrease oxidative damage, enhance mitophagy, maintain m, and boost adenosine triphosphate synthesis. These integrated approaches modulate fundamental pathogenic mechanisms of acute pancreatitis and improve outcomes in experimental settings. Conclusions. Pharmacological regulation of mitochondrial homeostasis offers a promising approach to targeted treatment of acute pancreatitis. Mitochondria-directed therapy may protect acinar cells and reduce the severity of systemic compli-cations.

гострий панкреатит; мітохондріальна дисфункція; мітохондріальна таргетна терапія; огляд

acute pancreatitis; mitochondrial dysfunction; mitochondria-targeted therapy; review

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