Isoflurane, but not sevoflurane, increases transendothelial albumin permeability in the isolated rat lung: role for enhanced phosphorylation of caveolin-1.
Isoflurane, but not sevoflurane, increases transendothelial albumin permeability in the isolated rat lung: role for enhanced phosphorylation of caveolin-1.
复制标题
异氟烷（而非七氟烷）增加离体大鼠肺中的跨内皮白蛋白通透性：增强 Caveolin-1 磷酸化的作用。
DOI：
10.1097/00000542-200604000-00023
复制
发表时间：
2006
期刊：
影响因子：
8.8
通讯作者：
Minshall,RichardD
中科院分区：
文献类型：
--
作者：
Hu,Guochang;Schwartz,DavidE;Shajahan,AyeshaN;Visintine,DavidJ;Salem,MRamez;Crystal,GeorgeJ;Albrecht,RonaldF;Vogel,StephenM;Minshall,RichardD
近年来研究表明，小窝介导的白蛋白跨内皮转运是调节微血管内皮白蛋白通透性的主要机制。作者研究了异氟烷和七氟烷对肺内皮白蛋白渗透性的影响，并评估了小窝支架蛋白，小窝蛋白-1，方法将分离的大鼠肺和培养的大鼠肺微血管内皮细胞（RLMVECs）暴露于1.0或2.0最小肺泡浓度（MAC）的异氟醚或七氟醚30 min。在离体肺中测定表面积乘积和毛细血管过滤系数。在RLMVECs中，在不存在和存在用2 mm甲基-β-环糊精（一种小窝破坏剂）预处理的情况下测量I-白蛋白的摄取和跨内皮转运。荧光标记的白蛋白的摄取，以及Src激酶和小窝蛋白-1的磷酸化，也被确定。在Y14 F-小窝蛋白-1突变体（nonphosphorylatable）表达RLMVECs，摄取的I-白蛋白和磷酸化的小窝蛋白-1.ResultsIn离体肺，2.0 MAC异氟烷增加I-白蛋白渗透性表面积产品48%，而不影响毛细血管过滤系数。在RLMVEC中，异氟烷使I-白蛋白的吸收增加了一倍多，并使I-白蛋白的跨内皮转运增加了54%。用甲基-β-环糊精预处理可阻断这些作用。异氟烷诱导的野生型RLMVECs中I-白蛋白摄取的增加在Y14 F-caveolin-1突变体表达细胞中被消除。异氟烷还导致Src和小窝蛋白-1磷酸化增加两倍。1.0 MAC异氟醚、1.0或2.0 MAC七氟醚均不影响白蛋白转运和小窝蛋白-1磷酸化的任何指标。结论异氟醚通过增强小窝蛋白介导的肺白蛋白摄取和转运，增加肺白蛋白的跨内皮通透性，但七氟醚无此作用。这种作用可能涉及小窝蛋白-1的磷酸化增强。
BackgroundCaveolae mediated transendothelial transport of albumin has recently been shown to be the primary mechanism regulating microvascular endothelial albumin permeability. The authors investigated the effects of isoflurane and sevoflurane on pulmonary endothelial albumin permeability and assessed the potential role of the caveolae scaffold protein, caveolin-1, in these effects.MethodsIsolated rat lungs and cultured rat lung microvessel endothelial cells (RLMVECs) were exposed to 1.0 or 2.0 minimum alveolar concentration (MAC) isoflurane or sevoflurane for 30 min. I-albumin permeability-surface area product and capillary filtration coefficient were determined in the isolated lungs. In RLMVECs, uptake and transendothelial transport of I-albumin were measured in the absence and presence of pretreatment with 2 mm methyl-beta-cyclodextrin, a caveolae-disrupting agent. Uptake of fluorescent-labeled albumin, as well as phosphorylation of Src kinase and caveolin-1, was also determined. In Y14F-caveolin-1 mutant (nonphosphorylatable) expressing RLMVECs, uptake of I-albumin and phosphorylation of caveolin-1 were evaluated.ResultsIn the isolated lungs, 2.0 MAC isoflurane increased I-albumin permeability-surface area product by 48% without affecting capillary filtration coefficient. In RLMVECs, isoflurane more than doubled the uptake of I-albumin and caused a 54% increase in the transendothelial transport of I-albumin. These effects were blocked by pretreatment with methyl-beta-cyclodextrin. The isoflurane-induced increase in uptake of I-albumin in wild-type RLMVECs was abolished in the Y14F-caveolin-1 mutant expressing cells. Isoflurane also caused a twofold increase in Src and caveolin-1 phosphorylation. Neither 1.0 MAC isoflurane nor 1.0 or 2.0 MAC sevoflurane affected any index of albumin transport or phosphorylation of caveolin-1.ConclusionIsoflurane, but not sevoflurane, increased lung transendothelial albumin permeability through enhancement of caveolae-mediated albumin uptake and transport in the isolated lung. This effect may involve an enhanced phosphorylation of caveolin-1.