Журнал "Гастроэнтерология" Том 59, №3, 2025

Актуальність. Порушення кальцієвого гомеостазу є центральною ланкою патогенезу гострого панкреатиту (ГП). Надлишкове накопичення Ca2+ у клітинах підшлункової залози ініціює каскад ушкоджень, що охоплює активацію зимогенів, мітохондріальну дисфункцію, енергетичне виснаження, стрес ендоплазматичного ретикулуму, некроз, апоптоз і розвиток запальної відповіді. Мета: проаналізувати сучасні дані щодо внутрішньоклітинної кальцієвої дисрегуляції при ГП з урахуванням ролі кальцієвої сигналізації в ушкодженні ацинарних, протокових, зірчастих і імунних клітин. Матеріали та методи. Проведено аналіз публікацій, відібраних з баз даних PubMed, Scopus і Google Scholar. Основну увагу приділено дослідженням кальцієвого обміну в ацинарних і протокових клітинах, кальцієвим каналам (Orai1, Piezo1, TRPV4), механізмам взаємодії з імунною системою. Результати. Встановлено, що внутрішньоклітинна кальцієва дисрегуляція є ключовою патофізіологічною подією при ГП. В ацинарних клітинах надмірне надходження Ca2+ активує іонні канали Orai1 та TRPV4, що сприяє хронічному підвищенню цитозольної концентрації кальцію. Це порушує функцію Ca2+-АТФаз, унеможливлює кліренс кальцію з цитозолю та створює умови для активації внутрішньоклітинних ферментів — насамперед трипсиногену. Кальцієве перевантаження мітохондрій призводить до відкриття перехідної пори мітохондрій, зниження мембранного потенціалу, зменшення продукції АТФ та запуску апоптозу або некрозу. У клітинах проток підшлункової залози патологічні коливання Ca2+ знижують експресію щільних контактів (ZO-1, E-кадгерин), підвищують проникність епітеліального бар’єра та створюють умови для трансдукції запального сигналу. У протокових клітинах перевантаження Ca2+ спричиняє пригнічення секреції рідини та HCO3–, порушення мітохондріальної функції та некроз. У зірчастих клітинах підшлункової залози кальцієві сигнали сприяють активації фібробластичного фенотипу з посиленою експресією TGF-β1, фібронектину та колагену І типу. Не менш важливою є кальцієво-опосередкована активація імунних клітин, зокрема макрофагів, що сприяє секреції прозапальних цитокінів і підтриманню системного запального каскаду. Висновки. Дисбаланс кальцію є критичним фактором ушкодження тканини підшлункової залози при ГП. Удосконалення розуміння кальцієвих сигналів відкриває перспективи для розробки нових методів лікування, спрямованих на запобігання прогресуванню та ускладненням захворювання.

Background. Disruption of calcium homeostasis is a central mechanism in the pathogenesis of acute pancreatitis (AP). Excessive accumulation of Ca2+ in pancreatic cells initiates a cascade of injuries, including zymogen activation, mitochondrial dysfunction, energy depletion, endoplasmic reticulum stress, necrosis, apoptosis, and the development of an inflammatory response. Objective: to analyze current data on intracellular calcium dysregulation in AP, with a focus on the role of calcium signaling in injury to acinar, ductal, stellate, and immune cells. Materials and methods. A literature review was conducted using PubMed, Scopus, and Google Scholar databases. The analysis focused on calcium metabolism in acinar and ductal cells, calcium channels (Orai1, Piezo1, TRPV4), and mechanisms of interaction with the immune system. Results. Intracellular calcium dysregulation is a key pathophysiological event in AP. In acinar cells, excessive Ca2+ influx via Orai1 and TRPV4 ion channels leads to sustained elevation of cytosolic calcium. This impairs Ca2+-ATPase activity, hampers effective calcium clearance from the cytosol, and promotes premature activation of intracellular enzymes, primarily trypsinogen. Mitochondrial calcium overload triggers the opening of the mitochondrial permeability transition pore, reduces membrane potential, decreases ATP production, and initiates apoptosis or necrosis. In pancreatic duct cells, pathological Ca2+ oscillations reduce the expression of tight junctions (ZO-1, E-cadherin), increase the permeability of the epithelial barrier, and create conditions for inflammatory signal transduction. In ductal cells, Ca2+ overload suppresses fluid and HCO3– secretion, impairs mitochondrial function, and induces necrosis. In pancreatic stellate cells, calcium signaling promotes activation of fibroblast phenotype characterized by increased expression of transforming growth factor β1, fibronectin, and type I collagen. Calcium-mediated activation of immune cells is equally important, particularly macrophages, which contributes to the release of proinflammatory cytokines and perpetuates the systemic inflammatory cascade. Conclusions. Calcium imbalance is a critical factor in pancreatic tissue damage in AP. Advancing the understanding of calcium signaling offers new perspectives for the development of new treatment strategies aimed at preventing disease progression and complications.

внутрішньоклітинний кальцій; кальцієва сигналізація; підшлункова залоза; гострий панкреатит

intracellular calcium; calcium signaling; pancreas; acute pancreatitis

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