PROTECTIVE EFFECT OF PROPOFOL ON FREE RADICAL INDUCED IMPAIRMENT OF VASCULAR SMOOTH MUSCLE REACTIVITY.

异丙酚对自由基引起的血管平滑肌反应性损伤的保护作用。

• 批准号: 10671756
• 负责人: KOBAYASHI Yutaka
• 金额: $ 1.73万
• 依托单位: KANAGAWA DENTAL COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671756/
• 关键词: PROPOFOL; VASCULAR SMOOTH MUSCLE; REACTIVE OXYGEN SPECIES; α-ADRENOCEPTOR; ENDOTHELIAL CELL; 内皮細胞

Propofol (2,6-diisopropylohenol) has been shown to attenuate oxidative stress-induced tissue injury. However, little is known concerning the effects of propofol on the reactive oxygen species-induced impairment of vascular reactivity. Therefore, this study was designed to examine the effect of propofol on reactive oxygen species-induced modification of the α-adrenoceptor mediated vascular contraction and in endothelium-dependent relaxation responses of the isolated blood vessels. The ring preparations of mesenteric artery from male albino rabbits were suspended in 10 ml organ baths containing modified Krebs-Ringer solution and changes in isometric force were measured. Effects of prior exposure the ring preparations to hydroxyl radical (HO) generated from Fenton's reagent (150 μM H_2O_2 plus 100 μM FeSO_4), hydrogen peroxide (H_2O_2 ; 150 μM) and FeSO_4 (100 μM ) on norepinephrine (NE ; 1μM)-induced contraction and acetylcholine (ACh ; 1 μM)-induced relaxation and protective effects of … More propofol were investigated. In addition, free radical scavenging property of propofol was also assessed using luminol-enhanced chemiluminescence method and electron spin resonance (ESR) spectroscopy. Prior exposure of ring preparations to HO and H_2O_2 inhibited NE-induced tension development to 47.0 ± 8.05 % and 40.2 ± 2.78 % of control values, respectively. Exposure the ring preparation to FeSO4 alone was without effect. While propofol, concentration of 10μM potentiated the NE-induced contraction by itself, it protected against the observed inhibitory effect on NE-induced contractile responses by Fenton's reagent and H_2O_2 to 97.4 ± 3.54 and 90.4 ± 4.20, respectively. Incubation of ring preparations with Krebs-Ringer solution containing Fenton's reagent and H_2O_2 inhibited ACh-induced relaxation to 79.8 ± 2.63 % and 73.0±2.77% of control values, respectively. Exposure the ring preparation to FeSO_4 alone was without effect. Propofol (10 μM, which has no effect on ACh-induced relaxation by itself) protected against the observed inhibitory effect on ACh-induced endothelium-dependent relaxation by HO or H_2O_2. Both Fenton's reagent- and H_2O_2-induced enhancements of luminol-chemilumionescence were attenuated by addition of propofol in a dose-dependent manner. Analysis of ESR spectroscopy provided the evidence that propofol and Diprivan【○!R】 in concentration of 1 and 10 μM, respectively, inhibited the formation of DMPO-HO spin adducts in a dose-dependently. Results obtained in present study demonstrated that clinically relevant concentration of propofol could protect against the impairment of vascular reactivity of isolated rabbit mesenteric artery induced by reactive oxygen species probably due to its scavenging ability of hydrogen peroxide. Less

丙泊酚（2，6-二异丙酚）已被证明可以减轻氧化应激诱导的组织损伤。然而，关于丙泊酚对活性氧诱导的血管反应性损伤的影响知之甚少。因此，本研究旨在研究丙泊酚对活性氧诱导的α-肾上腺素受体介导的血管收缩和离体血管内皮依赖性舒张反应的影响。取雄性白化病家兔肠系膜动脉环标本，悬于10 ml含改良Krebs-Ringer液的器官浴槽中，测定等长力的变化。预先暴露于由芬顿试剂（150 μM H_2O_2 + 100 μM FeSO_4）、过氧化氢（H_2O_2 ; 150 μM）和FeSO_4（100 μM）产生的羟自由基（HO）对去甲肾上腺素（NE ; 1μM）引起的收缩和乙酰胆碱（ACh ; 1 μM）引起的舒张的影响以及对血管的保护作用 ...更多信息 异丙酚进行了研究。此外，还采用鲁米诺增强化学发光法和电子自旋共振（ESR）法评价了异丙酚的清除自由基能力。预先暴露于HO和H_2O_2可抑制NE引起的张力形成，分别为对照值的47.0 ± 8.05%和40.2 ± 2.78%。将成形环制剂单独暴露于FeSO 4没有影响。10μM异丙酚对NE引起的收缩反应有增强作用，而对芬顿试剂和H_2O_2引起的收缩反应的抑制作用分别为97.4 ± 3.54和90.4 ± 4.20。用含有芬顿试剂和H_2O_2的Krebs-Ringer溶液孵育环标本，可分别抑制ACh引起的舒张，使其分别为对照值的79.8 ± 2.63%和73.0±2.77%。单独暴露于FeSO_4对环制备没有影响。异丙酚（10 μM，本身对ACh的舒张作用无影响）可对抗HO或H_2O_2对ACh的内皮依赖性舒张作用的抑制作用。异丙酚可剂量依赖性地减弱芬顿试剂和H_2O_2对鲁米诺荧光的增强作用。ESR波谱分析提供了异丙酚和得普利麻[○！1 μ M和10 μM的[R]对DMPO-HO自旋加合物的形成有剂量依赖性的抑制作用。本研究结果表明，临床相关浓度的异丙酚对活性氧引起的离体兔肠系膜动脉血管反应性损伤具有保护作用，其机制可能与其清除过氧化氢的能力有关。少

项目成果

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