• 系統編號 RN9705-0531
• 計畫中文名稱 靜脈麻醉藥物Propofol 抑制脂多醣引發巨噬細胞誘導型一氧化氮合成酵素基因表現之訊傳遞機轉探討
• 計畫英文名稱 Signal-Transducing Mechanism of Propofol-Involved Regulation of iNOS Gene Expression in Lipopolysaccharide-Activated Macrophages
• 主管機關 行政院國家科學委員會 • 計畫編號 NSC95-2314-B038-050
• 執行機構 台北醫學大學麻醉科
• 本期期間 9508 ~ 9607
• 報告頁數 14 頁 • 使用語言 中文
• 研究人員 張懷嘉 Chang, Huai-Chia
• 中文關鍵字 巨噬細胞; 一氧化氮合成酵素; 一氧化氮
• 英文關鍵字 Macrophages; Inducible nitric oxide synthase; Nitric oxide; Propofol; Lipopolysaccharide
• 中文摘要
一氧化氮(nitricoxide; NO)會參與調控巨噬細胞之功能，propofol 是臨床上廣泛被應用的一種靜脈麻醉藥物，此一研究旨在探討 propofol 抑制脂多醣引發巨噬細胞誘導型一氧化氮合成酵素(iNOS)的可能作用。Propofol 在臨床濃度下並不會造成巨噬細胞的死亡，但會抑制 lipopolysaccharide(LPS)所誘導的 NO 生成作用。免疫點墨(immunoblotting analysis)發現，propofol 會降低 LPS 所誘導的 iNOS 表現。LPS
所誘導增加的iNOS 基因表現量，亦會應 propofol 的處理而受到抑制。所以此一研究發現，propofol 會抑制巨噬細胞一氧化氮的生合
成，是經由調控iNOS 基因表現的機制。
• 英文摘要 Nitric oxide is an active oxidant that contributes to the physiology and pathophysiology of macrophages. Propofol has been widely used in intravenous anesthesia and also possess antioxidant and immunomodulating effects. This study is aimed to evaluate the effects of propofol on nitric oxide production in lipopolysaccharide-activated macrophages. exposure of macrophages to propofol (25, 50 and 75 .mu.M),
lipopolysaccharide (0.5, 1, 1.5 and 2 ng╱ml) or a combination of propofol and lipopolysaccharide did not affect cell viability. However, propofol at 100 .mu.M significantly led to cell death (P < 0.05). The levels of nitrite, an oxidative product of nitric oxide, were increased within
lipopolysaccharide-treated macrophages in a concentration-dependent manner (P < 0.01). While propofol could concentration-dependently decrease the lipopolysaccharide-enhanced nitrite levels (P < 0.01). Immunoblotting analysis revealed that lipopolysaccharide increased the protein level of inducible nitric oxide synthase (iNOS). Co-treatment of propofol and lipopolysaccharide significantly reduced this
lipopolysaccharide-induced iNOS protein (357 + 49 * 103 vs 92 + 6 * 103 arbitrary units, P < 0.01). Analysis by reverse transcriptase- polymerase chain reaction showed that lipopolysaccharide induced mRNA of iNOS, but the inductive effect was inhibited by propofol (95 +
7 * 102 vs 30 + 4 * 102 arbitrary units, P < 0.01). This study demonstrated that propofol, at therapeutic concentrations, could suppress NO biosynthesis through inhibiting iNOS expression in lipopolysaccharide-activated macrophages and the mechanism of suppression is at a pretranslational level.
