Ординатура / Хирургия / @xirurgi_2025 / @xirurgi_2025 - 1061 - файл

disordering is a key pathogenic mechanism initi­ating and driving pancreatitis. Although there is still much to be learnt about this mechanism, the ndings implicate organellar dysfunctions in mediating key pancreatitis responses, such as the intra-acinar trypsinogen activation, inamma­tion, and acinar cell death. In this review, we dis­cuss advancements in our understanding of the mechanisms of acinar cell events initiating pan­creatitis, with an emphasis on organelle disorders and approaches to alleviate the disease through normalizing organellar functions.

Because of the limited access to human pancre­atic tissue, studies addressing pancreatitis disease mechanisms make use of animal models. There are several well-characterized rodent models of pancreatitis, which reproduce pathologies of human disease. These models have greatly advanced our understanding of the cell biology and the molecular factors involved in the disease, which has allowed testing of potential therapeu­tic approaches. The characteristics of the models and methods of their development are described in detail in various reviews (e.g., Refs. 7, 14). The commonly used mouse AP models are those induced by administering supramaximal doses of caerulein (CER), an ortholog of the hormone cholecystokinin (CCK-8); by intraductal injec-

Inammation is a critical and universal compo­nent of pancreatitis [8, 53, 73, 75, 76]. In most patients, the acute inammatory response and pancreas damage ultimately resolve. However, in severe cases, the unremitting inammatory response results in a “cytokine storm,” develop­ment of the systemic inammatory response syn­drome, and ultimately multiple organ failure (especially the lung and kidney), a major cause of mortality among patients with AP [1, 8, 73, 77]. A key event initiating the inammatory response of pancreatitis is activation in the injured acinar cells of the proinammatory transcription factor NF-κB [22, 23, 73, 78, 79], which triggers mRNA expression of major proinammatory cytokines, including TNFα, IL-6, CCL2, CCL5, and others [24, 80–83]. These mediators recruit into the pan­creas neutrophils, monocytes, and macrophages, which secrete large amounts of proinammatory mediators, perpetuating acinar cell injury and thus creating a vicious circle of more tissue dam­age and more inammation [8, 53, 73, 76, 83–87]. In addition, damage-associated molecular pattern molecules (DAMPs) released from necrotic aci­nar cells cause inammasome activation and the resultant secretion of IL-1β and IL-18 by macro­phages inltrating the pancreas [75, 88–90].