| Project/Area Number |
11557093
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Digestive surgery
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| Research Institution | Osaka University |
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Principal Investigator |
NISHIDA Toshirou Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (40263264)
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| Co-Investigator(Kenkyū-buntansha) |
SEIYAMA Akitoshi Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70206605)
HIROTA Seiichi Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (50218856)
UCHIYAMA Yasuo Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (10049091)
ICHIKAWA Hajime Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (60303939)
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| Project Period (FY) |
1999 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥5,900,000 (Direct Cost: ¥5,900,000)
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| Keywords | Intestinal motility / Endotoxin / Interstitial Cells of Cajal / Macrophage / nitric oxide / iNOS / Infection / KIT |
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| Research Abstract |
Patients with severe sepsis frequently accompany gastrointestinal dysfunction such as paralytic ileus. The latter is thought to induce bacterial translocation, which may aggravate septic states of the patients. The mechanism of gastrointestinal motor dysfunction, however, is still unknown. Interstitial cells of Cajal (ICC) generate electric slow wave and thus are considered gastrointestinal pacemaker cells. We have investigated the mechanism of ICC injury under septic conditions using lipopolysaccharide (LPS)-injection model of mouse. Intraperitoneal injection of LPS decreased spontaneous intestinal movement, dose- and time- dependently. Similar results were obtained by measuring electric activity of electric slow wave. LPS also induced activation of macrophages and induction of iNOS in them. i.p. injection of LPS also caused decrease in KIT-positive cells in and around the myenteric plexus, LPS-induced decrease in both spontaneous intestinal movement and the KIT-positive cell number was restored by pretreatment of Gadlinium and addition of iNOS inhibitors. The additions of NO releaser, FK409, caused abrupt decrease in spontaneous intestinal movement in vitro. In vivo addition of FK409 caused decrease in both spontaneous intestinal movement and the KIT-positive cell number. The present results indicate that NO produced by iNOS, which is induced in activated macrophages by LPS, caused ICC injury, resulting in decrease in spontaneous intestinal movement and thus LPS-induced intestinal dysfunction.
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