Project/Area Number |
18590690
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Saga University |
Principal Investigator |
FUJIMOTO Kazuma Saga University, Saga Medical School Dept. of Gastrointestinal Endoscopy, Professor (50181392)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥3,730,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
|
Keywords | central nervous system / ileum / jejunum / metabolism / appetite / absorption / digestion / ischemia-reperfusion |
Research Abstract |
We have previously demonstrated that fasting and ischemia-reperfusion (I/R) induced apoptosis in rat intestinal mucosa. It is widely accepted that apoptosis is induced through two main pathways. This study aimed to compare apoptotic pathways following physiological conditions including fasting and I/R. Rats were divided into two groups: the I/R group involved occlusion of the superior mesenteric artery for 60 min, followed by 60 min reperfusion; while the fasting group involved fasting for 24 or 48 h. Additional rats were infused several physiological substances into the cerebro-ventricle. Intestinal apoptosis was assessed as% fragmented DNA, by electrophoresis, and by a TUNEL assay. Apoptotic proteins including death ligands/receptors, caspases were evaluated by Western blot analysis. Small intestinal mucosal height and mitochondrial dehydrogenase function were assessed. Physiological manipulation and I/R significantly induced intestinal apoptosis. Mucosal height was significantly decreased in fasting rats, and mitochondrial dysfunction was induced only by I/R. Expressions of Fas, FasL and TNFR1 were enhanced in rats of both groups. After I/R, expressions of cytochrome c and cleaved caspase-9 were significantly increased. In contrast, expressions of cleaved caspase-8 and cleaved caspase-3 increased in the physiological conditions. Physiological conditions promoted mucosal apoptosis via receptor-mediated type I apoptotic pathway in the rat small intestine, and I/R induced apoptosis via mitochondria-mediated type II pathway.
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