Research of Apoptosis of Intestinal Mucosa in Severe Acute Pancreatitis

细菌易位在重症急性胰腺炎的全身感染并发症中起重要作用。肠壁完整性的破坏被认为与细菌易位有关。首先，我们研究了实验性急性胰腺炎大鼠肠道通透性和细菌易位的变化。用3%脱氧胆酸钠逆行注入雄性Wistar大鼠胆管诱导重症坏死性胰腺炎。我们发现重症急性胰腺炎大鼠肠道通透性增加，细菌易位诱导。通过TUNEL染色和DNA片段化酶联免疫吸附法检测肠上皮细胞加速凋亡的机制。接下来，我们在该模型中测试了腹腔注射含氧全氟化学品对细菌易位的影响。治疗显著降低了细菌易位的发生率和数量，并增加了发生胰腺炎后肠系膜淋巴结的细菌菌落数量。细胞凋亡变化明显受到抑制。这些结果表明，腹腔注射含氧全氟化学物质可抑制重症急性胰腺炎诱导的肠上皮细胞凋亡和细菌易位。另一方面，人们认为caspase的级联激活参与了细胞凋亡的信号通路。我们在这个模型中检测了caspase抑制剂对细菌易位的影响。caspase抑制剂可降低凋亡诱导率，维持绒毛高度和隐窝深度，抑制肠通透性的增加。此外，caspase抑制剂减少内毒素转运到血液和细菌转运到肠系膜淋巴结，并提高死亡率。这些结果表明，抑制caspase激活可以通过维持肠黏膜的完整性来改善重症急性胰腺炎患者的内毒素血症和细菌移位。少

Bacterial translocation plays an important role for the systemic infectious complications in severe acute pancreatitis. The breakdown of the integrity of intestinal wall is believed to be implicated in bacterial translocation.First, we investigated about the gut permeability and bacterial translocation in rat experimental acute pancreatitis. Severe necrotizing pancreatitis was induced by retrograde injection of 3% sodium deoxycholate into the biliopancreatic ducts of male Wistar rats. We found that gut permeability was increased and that bacterial translocation was induced in rat severe acute pancreatitis. Moreover, as the mechanism, accelerated apoptosis of the intestinal epithelium was detected histochemically by TUNEL staining and biochemically by DNA fragmentation ELISA.Next, we tested the effect of intraperitoneal administration of oxygenated perfluorochemical on bacterial translocation in this model. The treatment significantly reduced incidence of bacterial translocation and num … More ber of bacterial colonies to the mesenteric lymph nodes after development of pancreatitis. The apoptotic changes were significantly suppressed by the treatment. These results suggest that intraperitoneal administration of oxygenated perfluorochemical inhibits apoptosis of intestinal epithelium and bacterial translocation induced in severe acute pancreatitis.On the other hand, it is believed that cascade of caspase activation is involved in the signaling pathway of apoptosis. We examined the effect of caspase inhibitor on bacterial translocation in this model. Administration of caspase inhibitor reduced the apoptosis induction rate, maintained the villous height and crypt depth, and suppressed the increase of gut permeability. Furthermore, caspase inhibitor reduced endotoxin translocation to blood and bacterial translocation to the mesenteric lymph nodes, and improved the mortality rate. These results indicate that inhibition of caspase activation ameliorated endotoxemia and bacterial translocation via the maintenance of the integrity of intestinal mucosa in severe acute pancreatitis. Less