Protective effects of propofol on lipopolysaccharide-activated endothelial cell barrier dysfunction
Protective effects of propofol on lipopolysaccharide-activated endothelial cell barrier dysfunction
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DOI：
10.1007/s00011-006-5116-0
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发表时间：
2006-09-01
影响因子：
6.7
通讯作者：
Chen, Z. Q.
中科院分区：
文献类型：
--
作者：
Gao, J.;Zhao, W. X.;Chen, Z. Q.
背景：异丙酚已广泛应用于静脉麻醉。它具有抗氧化和免疫调节作用。方法：体外培养的人脐静脉内皮细胞(HUVECs)：(1)不加任何添加剂(阴性对照)；(2)单用脂多糖(1和10mU g/ml)；(3)单用异丙酚(2 0mU g/ml)；(4)单用脂肪乳剂(异丙酚的一种溶剂)(2 0mU g/ml)；(V)脂多糖(10mUg/ml)+异丙酚(4和20mU/ml)；(6)脂多糖(10mUg/ml)+脂肪乳剂(20mUg/ml)。测定细胞通透性和丝状肌动蛋白(F-肌动蛋白)的变化。用Western印迹和免疫细胞化学方法分析硝基酪氨酸蛋白的表达和核因子-kappaB的活性。用逆转录-聚合酶链式反应分析内皮细胞内皮型一氧化氮合酶(ENOS)和诱导型一氧化氮合酶(INOS)的表达。结果：脂多糖显著增加内皮细胞的通透性，增加过氧化亚硝酸根的生成，促进F-肌动蛋白的解聚。脂多糖还能显著增加iNOS的mRNA表达，增加核因子-kappaB的蛋白水平，降低eNOS的mRNA表达(P<0.05)。两种浓度的异丙酚(4和20mU g/ml)均能显著抑制内毒素引起的细胞通透性增加和F-肌动蛋白结构的改变。异丙酚还可降低内毒素刺激的内皮细胞iNOS mRNA和NF-kappa B蛋白水平，增加eNOS mRNA表达(P<；0.05)。结论：异丙酚在治疗浓度和5倍治疗浓度下均能抑制内皮细胞中NF-kappa B的活化，对内毒素诱导的内皮细胞屏障功能障碍具有保护作用。
Background: Propofol has been widely used in intravenous anesthesia. It possesses antioxidant and immunomodulating effects. This study aimed to investigate whether propofol may attenuate lipopolysaccharide (LPS)-induced endothelial cell barrier dysfunction and the possible mechanisms of such modulation.Methods: Cultured human umbilical vein endothelial cells (HUVECs) were used to assess the following treatments: (i) no additives (negative control), (ii) LPS alone (1 and 10 mu g/ ml), (iii) propofol alone (20 mu g/ml), (iv) intralipid (a solvent of propofol) alone (20 mu g/ml), (v) LPS (10 mu g/ml) combination with propofol (4 and 20 mu g/ml) and (vi) LPS (10 mu g/ml) combination with intralipid (20 mu g/ml). Changes of cell permeability and filamentous actin (F-actin) were determined. Expression of nitrotyrosine proteins and activity of nuclear factor kappa B (NF-kappa B) were analyzed by Western blot and immunocytochemistry. Expression of endothelial nitric-oxide synthase (eNOS) and inducible nitric-oxide synthase (iNOS) were analyzed by reverse transcriptase-polymerase chain reaction.Results: LPS markedly increased the permeability of endothelial cells, the formation of peroxynitrite and depolymerization of F-actin in HUVECs. LPS also significantly increased mRNA of iNOS, protein level of NF-kappa B and decreased mRNA of eNOS (P < 0.05). Propofol at both concentrations (4 and 20 mu g/ml) significantly inhibited the LPS-induced increase in cell permeability and alteration in F-actin organization. Propofol also reduced the LPS-enhanced iNOS mRNA and NF-kappa B protein levels whilst it increased eNOS mRNA expression (P < 0.05).Conclusion: This study demonstrated that propofol, both at therapeutic concentrations and 5 times therapeutic concentrations, inhibited NF-kappa B activation in LPS-stimulated endothelial cells and was found to protect endothelial cells against LPS-induced barrier dysfunction.