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Research of Apoptosis of Intestinal Mucosa in Severe Acute Pancreatitis

重症急性胰腺炎肠粘膜细胞凋亡的研究

基本信息

批准号：
15591405
负责人：
UEDA Takashi
金额：
$ 1.34万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591405/
关键词：
severe acute pancreatitis apoptosis intestinal mucosa bacterial translocation 腸管上皮

项目摘要

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

细菌移位在重症急性胰腺炎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移位有关。首先，我们研究了大鼠实验性急性胰腺炎的肠道通透性和细菌移位。用3%脱氧胆酸钠逆行胰胆管注射诱导雄性Wistar大鼠重症坏死性胰腺炎。我们发现在大鼠重症急性胰腺炎中肠道通透性增加，并诱导细菌移位。此外，作为其机制，肠上皮细胞的加速凋亡进行了检测组织化学TUNEL染色和DNA片段化ELISA的生化。接下来，我们测试了在这个模型中的细菌移位的含氧全氟化合物的腹腔内给药的效果。治疗显著降低了细菌移位的发生率和数量， ...更多信息胰腺炎发生后肠系膜淋巴结的细菌菌落数。细胞凋亡的变化显着抑制治疗。这些结果表明，腹腔注射含氧全氟化合物可抑制重症急性胰腺炎诱导的肠上皮细胞凋亡和细菌移位，另一方面，caspase激活级联反应可能参与了凋亡的信号通路。我们研究了半胱天冬酶抑制剂对该模型中细菌移位的影响。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。Caspase抑制剂可减少内毒素向血液和肠系膜淋巴结的移位，提高死亡率。这些结果表明，抑制caspase的激活，改善内毒素血症和细菌移位，通过维持肠粘膜的完整性，在重症急性胰腺炎。少