Propofol-induced vascular permeability change is related to the nitric oxide signaling pathway and occludin phosphorylation
Propofol-induced vascular permeability change is related to the nitric oxide signaling pathway and occludin phosphorylation
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DOI：
10.1007/s11373-007-9164-4
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发表时间：
2007-09-01
影响因子：
11
通讯作者：
Lin, Chung-Ren
中科院分区：
文献类型：
--
作者：
Chen, Yi-Shen;Chen, Kuan-Hung;Lin, Chung-Ren
本研究旨在阐明异丙酚动脉内注射引起血管通透性改变导致组织水肿的机制。在大鼠股动脉注射模型上，研究了异丙酚诱导高通透性的机制。分别于注射异丙酚后15、30、45、60min测定肢体背侧皮肤伊文思蓝含量，测定血管通透性。用免疫印迹法检测了实验条件下紧密连接蛋白occludin、ZO-1和claudin-5的总含量。动脉注射异丙酚可引起大鼠后足血管通透性显著增加，且呈剂量依赖性。预先给予10 mg/kg的N-硝基-L-精氨酸甲酯(L-NAME)可明显抑制异丙酚攻击后血管通透性的变化。预先给予L精氨酸和硝普钠可增加异丙酚引起的通透性改变。动脉注射异丙酚后15min，闭塞蛋白磷酸化显著增加，且与时间相一致。LE的血管通透性改变。L-NAME部分逆转了阻断蛋白磷酸化的变化，而氨基胍与对照组相比无作用。我们的观察表明，一氧化氮(NO)是异丙酚诱导血管通透性的重要介质。阻滞素的磷酸化是异丙酚引起血管通透性改变的决定因素。一氧化氮合酶(NOS)抑制剂可能有助于治疗动脉内意外注射异丙酚，以减少任何不良反应。
The present study was undertaken to elucidate the mechanism of intra- arterial propofol- induced vascular permeability change resulting in tissue edema. The mechanism of propofol- induced hyperpermeability was examined in a rat femoral artery injection model. Vascular permeability was determined by measuring the Evans blue content of the dorsal skin of the infused limb at 15, 30, 45 and 60 min after propofol injection. The total content of the tight junction proteins occludin, ZO- 1 and claudin- 5 under experimental conditions was also determined by western blotting. Intra- arterial injection with propofol resulted in a marked dose-dependent increase in vascular permeability of the rat hindpaw. Pretreatment with 10 mg/ kg of N- nitro- L-arginine methyl ester ( L- NAME) but not aminoguanidine significantly inhibited the change in vascular permeability after challenge with propofol. Pretreatment with L- arginine and nitroprusside increased the propofol-induced permeability change. Intra- arterial injection of propofol significantly increased occludin phosphorylation after 15 min, which was consistent with the time pro. le of the vascular permeability change. L- NAME partially reversed the change in occludin phosphorylation, whereas aminoguanidine had no effect compared with that in the controls. Our observations indicate that nitric oxide ( NO) is an important mediator in the induction of vascular permeability induced by propofol. Occludin phosphorylation is a determining factor in the vascular permeability change induced by propofol. NO synthase ( NOS) inhibitors might be useful in the treatment of accidental intra- arterial injection of propofol, in the reduction of any adverse effects.