Criddle David N, McLaughlin Euan, Murphy John A, Petersen Ole H, Sutton Robert
MRC Group, Physiological Laboratory, University of Liverpool, Liverpool, UK.
Pancreatology. 2007;7(5-6):436-46. doi: 10.1159/000108960.
Acute pancreatitis is an increasingly common and sometimes severe disease for which there is little specific therapy. Chronic pancreatitis is a common and grossly debilitating sequel that is largely irreversible, whatever treatment is adopted. In the face of these burdens, the absence of specific treatments is a spur to research. The acinar cell is the primary target of injury from alcohol metabolites, bile, hyperlipidaemia, hyperstimulation and other causes. These induce abnormal, prolonged, global, cytosolic calcium signals, the prevention of which also prevents premature digestive enzyme activation, cytokine expression, vacuole formation and acinar cell necrosis. Such agents increase calcium entry through the plasma membrane and/or increase calcium release from intracellular stores, shown to result from effects on calcium channels and calcium pumps, or their energy supply. A multitude of signalling mechanisms are activated, diverted or disrupted, including secretory mechanisms, lysosomal regulators, inflammatory mediators, cell survival and cell death pathways, together with or separately from calcium. While recent discoveries have increased insight and suggest prophylaxis or treatment targets, more work is required to define the mechanisms and interactions of cell signalling pathways in the pathogenesis of pancreatitis.
急性胰腺炎是一种日益常见且有时较为严重的疾病，对此几乎没有特效疗法。慢性胰腺炎是一种常见且严重致残的后遗症，无论采取何种治疗方法，在很大程度上都是不可逆的。面对这些负担，缺乏特效治疗方法促使人们进行研究。腺泡细胞是酒精代谢产物、胆汁、高脂血症、过度刺激及其他病因所致损伤的主要靶点。这些因素会诱发异常、持续、广泛的胞质钙信号，而预防这种信号也能防止消化酶过早激活、细胞因子表达、液泡形成及腺泡细胞坏死。此类因素通过质膜增加钙内流和/或增加细胞内钙库的钙释放，这已表明是对钙通道、钙泵或其能量供应产生影响的结果。众多信号传导机制被激活、转向或破坏，包括分泌机制、溶酶体调节因子、炎症介质、细胞存活及细胞死亡途径，这些机制与钙共同作用或独立于钙发挥作用。尽管最近的发现增进了人们的认识并提示了预防或治疗靶点，但仍需要更多工作来明确细胞信号传导通路在胰腺炎发病机制中的作用机制及相互作用。
