analysis of cytoprotection by COX-2 induced in gastric mucosa : influence by selective COX-2 inhibitors

COX-2 在胃粘膜中诱导的细胞保护分析：选择性 COX-2 抑制剂的影响

• 批准号: 12670526
• 负责人: MIYAKE Kazumasa
• 金额: $ 1.73万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670526/
• 关键词: 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

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.

目的：内源性和外源性前列腺素（pg）已被证明有助于减轻随后给予的刺激引起的胃损伤。本研究的目的是阐明预处理诱导的环氧合酶-2 （COX-2）蛋白是否参与了小鼠后续乙醇性胃损伤的预防。方法：小鼠经酸化乙醇或生理盐水预处理，每8 h免疫组化检测胃内COX-2蛋白表达。酸化乙醇预处理24小时后给予95%乙醇，观察胃粘膜损伤的宏观和组织学变化。研究了NS-398或吲哚美辛对95%乙醇损伤的影响。结果：酸化乙醇预处理诱导胃粘膜固有层巨噬细胞COX-2蛋白表达，预处理后24 h达到峰值。95%乙醇引起胃粘膜损伤。酸化乙醇和生理盐水预处理小鼠的损伤程度无显著差异。然而，NS-398只在酸化乙醇预处理的小鼠中加重了乙醇引起的损伤，而吲哚美辛加重了组织学上评估的损伤，与预处理无关。结论：预处理诱导的COX-2和COX-1似乎通过减少后续刺激引起的损伤参与了防御机制。

项目成果

三宅一昌, 坂本長逸: "症例から学ぶ胃の病理 9.消化性潰瘍総論と特殊胃潰瘍"Modem physician. 1461-1465 (2001)

Kazumasa Miyake、Choitsu Sakamoto：“从病例 9 中学习胃病理学。消化性溃疡和特殊胃溃疡的概述”现代医师 1461-1465 (2001)。

Miyake K, Tsukui T, Futagami S, Tatsuguchi A, Shinoki K, Hiratsuka T, Iizumi T, Nagata K, Shinji Y, Wada K, Yamada N, Kobayashi M, Sakamoto C.: "Effect of acid suppression therapy on development of gastric erosions after cure of Helicobacter pylori infect

Miyake K、Tsukui T、Futagami S、Tatsuguchi A、Shinoki K、Hiratsuka T、Iizumi T、Nagata K、Shinji Y、Wada K、Yamada N、Kobayashi M、Sakamoto C.：“抑酸治疗对胃病发展的影响

Futagami S, Miyake K et al.: "Inhibition of helicobacter pylori-induced cox-2 agravates NSAID-caused gastric damage in Mongolian gerbils"Aliment Pharmacol Ther. (in press). (2002)

Futagami S、Miyake K 等人：“抑制幽门螺杆菌诱导的 cox-2 会加重蒙古沙鼠中 NSAID 引起的胃损伤”Aliment Pharmacol Ther。

Tsukui T, Miyake K et al.: "Aging increases and duodenal ulcer reduces the risk for intestinal metaplasia of the gastric corpus in Japanese patients with dyspepsia"J of Gastroenterology and Hepatology. 16. 15-21 (2001)

Tsukui T、Miyake K 等人：“衰老和十二指肠溃疡降低了日本消化不良患者胃体肠上皮化生的风险”J of Gastroenterology and Hepatology。

三宅一昌, 坂本長逸: "症例から学ぶ胃の病理 9.消化性潰瘍総論と特殊胃潰瘍"Modern physician. 1461-5 (2001)

Kazumasa Miyake、Choitsu Sakamoto：“从病例 9 中学习胃病理学。消化性溃疡和特殊胃溃疡的概述” 现代医师 1461-5 (2001)。