Pathophysiology of alcohol-induced pancreatitis
Pathophysiology of alcohol-induced pancreatitis
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DOI：
10.1097/00006676-200311000-00003
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发表时间：
2003-11-01
期刊：
影响因子：
2.9
通讯作者：
Krüger, B
中科院分区：
文献类型：
--
作者：
Lerch, MM;Albrecht, E;Krüger, B
过量的酒精摄入是急性和慢性胰腺炎的常见危险因素。乙醇可以通过多种方式导致胰腺炎的发作;最近发现的是其对胰腺内消化酶激活的影响，通过使腺泡细胞对病理刺激敏感或刺激十二指肠I细胞释放促分泌素（胆囊收缩素）。细胞生物学和分子生物学技术的最新进展使我们能够以以前认为不可能的方式解决消化酶激活所涉及的细胞内事件。使用这些新技术的研究发现：（a）与其在小肠中的作用相反，胰蛋白酶不一定参与其它消化蛋白酶如前弹性蛋白酶的过早细胞内活化;（B）胰蛋白酶原不自动细胞内活化，而是主要由溶酶体水解酶组织蛋白酶B活化;和（c）胰蛋白酶在胰内蛋白酶级联中的作用最可能是涉及包括胰蛋白酶本身的活性消化蛋白酶的降解而不是活化。这些研究，以及已经解决了突变型胰蛋白酶在遗传性胰腺炎发病中的作用的调查，表明胰蛋白酶可能不是触发胰腺炎的关键，但可能对一些其他消化蛋白酶的作用具有保护作用。虽然不同消化酶在引发胰腺炎中的具体作用仍然是一个有争议的问题和正在进行的研究的主题，但实验证据表明，乙醇可以直接干扰消化酶原激活所涉及的过程。
Excessive ethanol consumption is a common risk factor for acute and chronic pancreatitis. Ethanol could lead to the onset of pancreatitis in a number of ways; the most recently discovered is its effect on intrapancreatic digestive enzyme activation, by either sensitizing acinar cells to pathologic stimuli or stimulating the release of a secretagogue ( cholecystokinin) from duodenal I cells. Recent advances in cell biologic and molecular techniques have permitted us to address the intracellular events involved in digestive enzyme activation in a manner that was previously considered impossible. Investigations that used these novel techniques found that ( a) trypsin is, in contrast to its role in the small intestine, not necessarily involved in the premature intracellular activation of other digestive proteases such as proelastase; (b) trypsinogen does not autoactivate intracellularly but is instead largely activated by the lysosomal hydrolase cathepsin B; and ( c) the role of trypsin in the intrapancreatic protease cascade is most likely one that involves the degradation, rather than the activation, of active digestive proteases including trypsin itself. These studies, as well as investigations that have addressed the role of mutant trypsin in the disease onset of hereditary pancreatitis, suggest that trypsin may not be critical for triggering pancreatitis but might have a protective role against the action of some of the other digestive proteases. While the specific role of different digestive enzymes in initiating pancreatitis is still a matter of debate and the topic of ongoing investigations, experimental evidence suggests that ethanol can directly interfere with the processes involved in digestive zymogen activation.