Project/Area Number |
12670526
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Nippon Medical School |
Principal Investigator |
MIYAKE Kazumasa Nippon Medical School, Third department of Internal Medicine, Assistant, 医学部, 助手 (60247012)
|
Co-Investigator(Kenkyū-buntansha) |
SAKAMOTO Choitsu Nippon Medical School, Third department of Internal Medicine, Assistant, 医学部, 教授 (30196092)
|
Project Period (FY) |
2000 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | cyclooxygenase-2 / selective COX-2 inhibitors / gastric mucosal injury / ethanol / NS 398 / Indomethacin / Cyclooxygenase / VEGF / 粘膜保護作用 / 選択的COX2阻害剤 / 胃 |
Research Abstract |
Purpose : Endogenous and exogenous prostaglandins (PGs) have been shown to contribute to reduce gastric injury caused by irritants given subsequently. The aim of the study is to clarify whether cyclooxygenase-2 (COX-2) protein induced by pretreatment is involved in prevention of subsequent ethanol-caused gastric injury in mice. Methods : Mice were pretreated with acidified ethanol or saline and then COX-2 protein expression was immunohistochemically determined at every 8 hours in the stomachs. Mice were administered 95 % ethanol 24 hours after acidified ethanol pretreatment and gastric mucosal damages were evaluated macroscopically and histologically. The effects of NS-398 or indomethacin on 95 % ethanol-caused damage were also examined. Results : Acidified ethanol pretreatment induced COX-2 protein expression in lamina propria macrophages of the gastric mucosa with its peak level 24 hours after the pretreatment. 95 % ethanol caused gastric mucosal damages. The degree of the damages was not different between mice pretreated with acidified ethanol and saline. However, NS-398 aggravated ethanol-caused damages only in mice pretreated with acidified ethanol, while indomethacin aggravated the damages evaluated histologically Irrespective of the pretreatment. Conclusions : The pretreatment- induced COX-2 in addition to COX-1 seems to be involved in the defense mechanism through minimizing damages caused by a subsequent irritant.
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