Study on rales of cyclooxygenase-2 in acute inflammation

急性炎症中环氧合酶2的啰音研究

• 批准号: 06672276
• 负责人: HARADA Yoshiteru
• 金额: $ 1.41万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06672276/
• 关键词: carrageenin-induced pleurisy; prostaglandins; cyclooxygenase-2; aspirin; NS-398; nimesulide; dexamethasone; anti-inflammatory drugs; ニメスリド; カラグニン胸膜炎; SC-58125; 非ステロイド性抗炎症薬

Using rat carrageenin-induced pleurisy as an acute inflammatory model, the following results were obtained. 1) COX-2 mRNA and protein were detectable in cells in the pleural exudate. Change of COX-2 protein level was closely paralleled those of plasma exudation rate and PGE2 levels in the exudate. COX-1 was also detectable, but kept almost the same level throughout the course of the pleurisy. 2) The selective COX-2 inhibitors NS-398, nimesulide and SC-58125 suppressed the inflammatory reaction an caused a marked decrease in the level of PGE2 but not in those of TXB2 and 6-keto-PGF1alpha. These results suggest that the COX-2 expressed in the pleural exudate cells may be involved in PGE2 formation at the site of inflammation. 3) Dexamethasone (0.3-30 mg/kg, i.p.) markedly suppressed leukocyte infiltration and plasma exudation. Although the agent also suppressed COX-2 expression at higher doses (>3 mg/kg), it never affected at a lower dose (0.3 mg/kg). These results suggest the involvement of other mechanism (s) than inhibition of COX-2 expression as mechanisms of anti-inflammatory steroids. 4) At 5 hr after carrageenin injection, 92.0% of the cells were PMN leukocytes with a small number of mononuclear leukocytes. Both PMN and mononuclear leukocytes expressed PGHS-2, but there exist difference in pattern of COX-2 expresion. The most mononuclear cells expressed COX-2 intensively, but small number of PMN leukocytes expressed it intensively. Thus both types of cells may equally contribute to the total amount of COX-2 in the inflammatory site. 5) Among TNFalpha, IL-1alpha, IL-1beta, IL-6, CINC-1 and MCP-1, only TNFalpha (10 pmole) induced COX-2 expression by intrapleural injection.

以大鼠角叉菜胶性胸膜炎为急性炎症模型，得到如下结果：1)胸膜渗出细胞中检测到COX-2 mRNA和蛋白。COX-2蛋白水平的变化与血浆渗出率和渗出液中PGE2水平的变化密切相关。COX-1也可检测到，但在整个胸膜炎过程中几乎保持相同的水平。2)选择性COX-2抑制剂NS-398、尼美舒利和SC-58125均能抑制炎症反应，显著降低PGE2水平，但不影响TXB2和6-酮- pgf1 α水平。提示胸膜渗出细胞中COX-2的表达可能参与了炎症部位PGE2的形成。3)地塞米松（0.3 ~ 30mg /kg, ig）显著抑制白细胞浸润和血浆渗出。虽然该药物在高剂量（3 mg/kg）下也抑制COX-2的表达，但在低剂量（0.3 mg/kg）下则不受影响。这些结果提示除了抑制COX-2表达外，还有其他机制参与抗炎类固醇的作用机制。4)角叉菜胶注射后5小时，92.0%的细胞为PMN白细胞，少量单核白细胞。PMN和单核白细胞均表达PGHS-2，但COX-2的表达模式存在差异。COX-2在大多数单核细胞中有高表达，但在PMN白细胞中有少量高表达。因此，两种类型的细胞可能同样有助于炎症部位COX-2的总量。5)胸膜内注射TNFalpha、il -1 α、il -1 β、IL-6、cinc1和MCP-1中，只有TNFalpha（10摩尔）诱导COX-2表达。

项目成果

Ko Hatanaka: "Contributions of leukocytes and cyclooxygenase subtypes in generation of prostaglandins in rat carrageenin-indnced plenrisy" Mocro ciraelation Annual. 11. 143-144 (1995)

Ko Hatanaka：“白细胞和环氧合酶亚型在大鼠角叉胶诱导的前列腺素生成中的贡献”Mocro ciraelation Annual。

Michiko Kawamura: "Evaluation of plasma 11-dehydro-thromboxane B_2 as an indicator for thromboxane A_2 synthesis in vivo in laboratory animals" Thromb. Res.77. 465-474 (1995)

Michiko Kawamura：“评估血浆 11-脱氢血栓素 B_2 作为实验动物体内血栓素 A_2 合成的指标” Thromb。

Yoshiteru Harada: "Role of prostaglandin H syrthase-2 in prostaglandin E_2 formation in rat corrageenin-induced pleurisy" Prostaglandins. 51. 19-33 (1996)

Yoshiteru Harada：“前列腺素 H 合酶 2 在大鼠角叉菜胶诱导的胸膜炎中前列腺素 E_2 形成中的作用”前列腺素。

Yoshiteru Harada: "Role of prostaglandin H synthase-2 in proatsglandin E_2 formation in rat carrageenin-induced plenrisy" Prostaglandins. (in press). (1996)

Yoshiteru Harada：“前列腺素 H 合酶 2 在大鼠角叉胶诱导的前列腺素 E_2 形成中的作用”前列腺素。

Michiko Kawamura: "Evaluation of plasma II-dehydro-thromboxane B_2 as an indicator for thromboxane A2 synthesis in vivo in laboratory animals" Thromb.Res.77. 465-474 (1995)

Michiko Kawamura：“血浆 II-脱氢血栓烷 B_2 作为实验动物体内血栓素 A2 合成指标的评估”Thromb.Res.77。