Sci Transl Med：“自食性”消化酶与器官衰竭有关

　　据一项新的研究报告，胰腺酶渗漏到肠内可导致休克，这是一种与败血症和多器官衰竭有关系的威胁生命的内科疾病。对于休克，目前还没有被认可的治疗方式。这些发现为那些因创伤、手术、心肌梗死及其它导致器官衰竭而进入重症监护病房的患者提供了一种可能的帮助治疗他们的方法。消化酶是在胰腺中制造的。在健康人中，极少的消化酶会跨过黏膜屏障逸入肠壁。这种场景可能就是在休克时所发生的情况。消化酶渗漏到肠壁内并开始降解肠组织，导致炎症和器官损坏，就像是Frank DeLano及其同事在大鼠试验中所展示的那样。这些酶可从肠道渗漏至血流、肝、肺及肾中并开始对那些器官也造成损害。为了阻止这一大灾祸，研究人员直接将消化酶的化学阻滞剂灌注到大鼠的小肠内。与未经治疗的动物相比，他们观察到对器官的损害变少了，大鼠的恢复加快了，且由休克所致的死亡显著减少。尽管需要在临床试验中做进一步的测试，但医生们最近在治疗一名病情危重的感染性休克病人的过程当中将其作为最后一搏的尝试而使用了这种方法。令人鼓舞的是，他们通过给予患者抑制消化酶的药物而挽救了该患者的生命。

Pancreatic Digestive Enzyme Blockade in the Intestine Increases Survival After Experimental Shock

ABSTRACT

Shock, sepsis, and multiorgan failure are associated with inflammation, morbidity, and high mortality. The underlying pathophysiological mechanism is unknown, but evidence suggests that pancreatic enzymes in the intestinal lumen autodigest the intestine and generate systemic inflammation. Blocking these enzymes in the intestine reduces inflammation and multiorgan dysfunction. We investigated whether enzymatic blockade also reduces mortality after shock. Three rat shock models were used here: hemorrhagic shock, peritonitis shock induced by placement of cecal material into the peritoneum, and endotoxin shock. One hour after initiation of hemorrhagic, peritonitis, or endotoxin shock, animals were administered one of three different pancreatic enzyme inhibitors—6-amidino-2-naphtyl p-guanidinobenzoate dimethanesulfate, tranexamic acid, or aprotinin—into the lumen of the small intestine. In all forms of shock, blockade of digestive proteases with protease inhibitor attenuated entry of digestive enzymes into the wall of the intestine and subsequent autodigestion and morphological damage to the intestine, lung, and heart. Animals treated with protease inhibitors also survived in larger numbers than untreated controls over a period of 12 weeks. Surviving animals recovered completely and returned to normal weight within 14 days after shock. The results suggest that the active and concentrated digestive enzymes in the lumen of the intestine play a central role in shock and multiorgan failure, which can be treated with protease inhibitors that are currently available for use in the clinic.