Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California.
Division of Gastroenterology, Department of Medicine, Department of Veterans Affairs and David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California.
Gastroenterology. 2019 May;156(7):1941-1950. doi: 10.1053/j.gastro.2018.11.082. Epub 2019 Jan 18.
Acute pancreatitis is an inflammatory disorder of the exocrine pancreas associated with tissue injury and necrosis. The disease can be mild, involving only the pancreas, and resolve spontaneously within days or severe, with systemic inflammatory response syndrome-associated extrapancreatic organ failure and even death. Importantly, there are no therapeutic agents currently in use that can alter the course of the disease. This article emphasizes emerging findings that stressors (environmental and genetic) that cause acute pancreatitis initially cause injury to organelles of the acinar cell (endoplasmic reticulum, mitochondria, and endolysosomal-autophagy system), and that disorders in the functions of the organelles lead to inappropriate intracellular activation of trypsinogen and inflammatory pathways. We also review emerging work on the role of damage-associated molecular patterns in mediating the local and systemic inflammatory response in addition to known cytokines and chemokine pathways. In the review, we provide considerations for correction of organelle functions in acute pancreatitis to create a discussion for clinical trial treatment and design options.
急性胰腺炎是一种与胰腺组织损伤和坏死相关的胰腺外分泌炎症性疾病。该疾病可能较轻，仅累及胰腺，数天内可自发缓解，也可能较严重，出现全身炎症反应综合征相关的胰外器官功能衰竭，甚至死亡。重要的是，目前尚无可改变疾病进程的治疗药物。本文强调了一些新发现，即导致急性胰腺炎的应激源（环境和遗传）最初会导致胰腺泡细胞的细胞器（内质网、线粒体和内溶酶体-自噬系统）损伤，细胞器功能障碍会导致胰蛋白酶原和炎症途径的细胞内激活不当。我们还回顾了关于损伤相关分子模式在介导局部和全身炎症反应中的作用的新工作，以及已知的细胞因子和趋化因子途径。在综述中，我们对纠正急性胰腺炎中细胞器功能的考虑因素进行了讨论，为临床试验治疗和设计方案提供了讨论依据。
