Clemens Dahn L, Schneider Katrina J, Arkfeld Christopher K, Grode Jaclyn R, Wells Mark A, Singh Shailender
Dahn L Clemens, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198-8098, United States.
World J Gastrointest Pathophysiol. 2016 Feb 15;7(1):48-58. doi: 10.4291/wjgp.v7.i1.48.
Acute pancreatitis is a necro-inflammatory disease of the exocrine pancreas that is characterized by inappropriate activation of zymogens, infiltration of the pancreas by inflammatory cells, and destruction of the pancreatic exocrine cells. Acute pancreatitis can progress to a severe life-threatening disease. Currently there is no pharmacotherapy to prevent or treat acute pancreatitis. One of the more common factors associated with acute pancreatitis is alcohol abuse. Although commonly associated with pancreatitis alcohol alone is unable to cause pancreatitis. Instead, it appears that alcohol and its metabolic by-products predispose the pancreas to damage from agents that normally do not cause pancreatitis, or to more severe disease from agents that normally cause mild pancreatic damage. Over the last 10 to 20 years, a tremendous amount of work has defined a number of alcohol-mediated biochemical changes in pancreatic cells. Among these changes are: Sustained levels of intracellular calcium, activation of the mitochondrial permeability transition pore, endoplasmic reticulum stress, impairment in autophagy, alteration in the activity of transcriptional activators, and colocalization of lysosomal and pancreatic digestive enzymes. Elucidation of these changes has led to a deeper understanding of the mechanisms by which ethanol predisposes acinar cells to damage. This greater understanding has revealed a number of promising targets for therapeutic intervention. It is hoped that further investigation of these targets will lead to the development of pharmacotherapy that is effective in treating and preventing the progression of acute pancreatitis.
急性胰腺炎是一种外分泌性胰腺的坏死性炎症性疾病，其特征为酶原的不适当激活、炎症细胞浸润胰腺以及胰腺外分泌细胞的破坏。急性胰腺炎可发展为严重的危及生命的疾病。目前尚无预防或治疗急性胰腺炎的药物疗法。与急性胰腺炎相关的较常见因素之一是酗酒。虽然酗酒通常与胰腺炎相关，但仅酒精本身并不能导致胰腺炎。相反，酒精及其代谢副产物似乎使胰腺易受通常不会引起胰腺炎的因素的损害，或使胰腺对通常引起轻度胰腺损伤的因素产生更严重的疾病。在过去10至20年中，大量工作已明确了胰腺细胞中一些酒精介导的生化变化。这些变化包括：细胞内钙水平持续升高、线粒体通透性转换孔激活、内质网应激、自噬受损、转录激活因子活性改变以及溶酶体和胰腺消化酶共定位。对这些变化的阐明使人们对乙醇使腺泡细胞易受损伤的机制有了更深入的了解。这种更深入的了解揭示了一些有前景的治疗干预靶点。希望对这些靶点的进一步研究将导致开发出有效治疗和预防急性胰腺炎进展的药物疗法。
