2004 Fiscal Year Final Research Report Summary
Research of Apoptosis of Intestinal Mucosa in Severe Acute Pancreatitis
| Project/Area Number |
15591405
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Kobe University |
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Principal Investigator |
UEDA Takashi Kobe University, Graduate School of Medical Science, Gastroenterological Surgery, Assistant, 医学部附属病院, 助手 (80346262)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEYAMA Yoshifumi Kinki University, School of Medicine, Surgery, Associate Professor, 医学部, 助教授 (70263374)
KURODA Yoshikazu Kobe University, Graduate School of Medical Science, Gastroenterological Surgery, Professor, 大学院・医学系研究科, 教授 (70178143)
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| Project Period (FY) |
2003 – 2004
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| Keywords | severe acute pancreatitis / apoptosis / intestinal mucosa / bacterial translocation |
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| Research Abstract |
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
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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
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