From the, Departments of Medicine and Physiology, University of Toronto, Toronto, ON, Canada.
Alcohol Clin Exp Res. 2020 Apr;44(4):777-789. doi: 10.1111/acer.14304. Epub 2020 Mar 1.
Alcohol is a major cause of acute and chronic pancreatitis. There have been some recent advances in the understanding of the mechanisms underlying alcoholic pancreatitis, which include perturbation in mitochondrial function and autophagy and ectopic exocytosis, with some of these cellular events involving membrane fusion soluble N-ethylmaleimide-sensitive factor receptor protein receptor proteins. Although new insights have been unraveled recently, the precise mechanisms remain complex, and their finer details have yet to be established. The overall pathophysiology of pancreatitis involves not only the pancreatic acinar cells but also the stellate cells and duct cells. Why only some are more susceptible to pancreatitis and with increased severity, while others are not, would suggest that there may be undefined protective factors or mechanisms that enhance recovery and regeneration after injury. Furthermore, there are confounding influences of lifestyle factors such as smoking and diet, and genetic background. Whereas alcohol and smoking cessation and a generally healthy lifestyle are intuitively the advice given to these patients afflicted with alcoholic pancreatitis in order to reduce disease recurrence and progression, there is as yet no specific treatment. A more complete understanding of the pathogenesis of pancreatitis from which novel therapeutic targets could be identified will have a great impact, particularly with the stubbornly high fatality (>30%) of severe pancreatitis. This review focuses on the susceptibility factors and underlying cellular mechanisms of alcohol injury on the exocrine pancreas.
酒精是急性和慢性胰腺炎的主要病因。近年来，人们对酒精性胰腺炎的发病机制有了一些新的认识，包括线粒体功能和自噬及异位胞吐的紊乱，其中一些细胞事件涉及膜融合可溶性 N-乙基马来酰亚胺敏感因子受体蛋白受体蛋白。尽管最近有了新的见解，但确切的机制仍然很复杂，其更细微的细节尚未确定。胰腺炎的整体病理生理学不仅涉及胰腺腺泡细胞，还涉及星状细胞和胆管细胞。为什么只有一些细胞更容易发生胰腺炎，而且严重程度更高，而另一些细胞则不会，这表明可能存在尚未确定的保护因素或机制，以增强损伤后的恢复和再生。此外，还存在生活方式因素（如吸烟和饮食）和遗传背景的混杂影响。虽然戒酒和戒烟以及健康的生活方式通常是给患有酒精性胰腺炎的这些患者的建议，以减少疾病复发和进展，但目前还没有特定的治疗方法。更全面地了解胰腺炎的发病机制，从中可以确定新的治疗靶点，这将产生重大影响，特别是对于重症胰腺炎死亡率（>30%）居高不下的情况。本文重点讨论了酒精对胰腺外分泌的损伤的易感性因素和潜在的细胞机制。
