丙泊酚对内毒素诱导内皮细胞通透性和细胞骨架的影响  

Effects of propofol on the changes in cytoskeleton and cellular permeability of human umbilical vascular endothelial cells monolayer induced by lipopolysaccharide

作　　者：高巨[1] 招伟贤[1] 周罗晶[2] 刘东[3] 曾邦雄[3] 姚尚龙[3] 

机构地区：[1]广州中医药大学第二附属医院（广东省中医院）麻醉科,510120 [2]广州中医药大学第二附属医院（广东省中医院）临床流行病室,510120 [3]华中科技大学同济医学院附属协和医院麻醉科

出　　处：《中国危重病急救医学》2007年第12期717-720,共4页Chinese Critical Care Medicine

基　　金：广东省中医药管理局基金资助项目（2050069）;广东省医学科研基金资助项目（A2005269）

摘　　要：目的研究丙泊酚对内毒素诱导人脐静脉内皮细胞（HUVECs）单层通透性和细胞骨架变化的影响。方法HUVECs细胞株培养鉴定后随机分7组，每组5份，施以相应处理：①对照组（C组）；②内毒素组：脂多糖（LPS）终浓度分别为1mg／L和10mg／L（LPS1组及LPS10组）；③丙泊酚组（P4组）：丙泊酚终浓度为4mg／L；④脂质溶剂组（14组）：脂质溶剂体积和浓度同P4组；⑤丙泊酚＋内毒素组（P4＋LPS10组）：丙泊酚和LPS的终浓度分别为4mg／L和10mg／L；⑥脂质溶剂＋内毒素组（14＋LPS10组）：脂质溶剂和LPS的终浓度分别为4mg／L和10mg／L。孵育6h后测定内皮细胞单层滤过系数（Kf）和蛋白质渗透压反射系数（σ）以反映内皮细胞单层通透性的变化；荧光染色法测定内皮细胞纤维状肌动蛋白（F-actin）及细胞化学技术检测硝基酪氨酸（NT）的表达。结果与C组比较，LPS作用使内皮细胞Kf增加，蛋白质σ减少（P均〈0．01），F-actin含量降低，NT蛋白表达显著增加（P〈0．01），尤以高浓度LPS作用更明显。P4＋LPS10组可显著减少LPS引起的内皮细胞Kf和蛋白质σ的变化，抑制10mg／L LPS引起的F-actin解聚和NT蛋白增加（P均〈0．01）。而I4＋LPS10组无上述保护效应。结论丙泊酚可减少LPS所致单层内皮细胞通透性的增加，这种保护作用可能是通过抑制LPS引起的过氧亚硝基阴离子（ONOO^-）过量生成，从而稳定内皮细胞骨架来实现的。Objective To investigate the effects of propofol on the changes in actin cytoskeleton and permeability of cultured human umbilical vascular endothelial cells （HUVECs） monolayer induced by lipopolysaccharide （LPS）. Methods HUVECs were randomly assigned to one of the following seven groups： no additives （negative control）, LPS alone （1 mg/L and 10 mg/L）, propofol alone （4 mg/L）, introlipid alone, LPS （10 mg/L） combination with propofol （4 mg/L） and LPS （10 mg/L） together with introlipid （4 mg/L）. Changes in filtration coefficients （Kf） and osmotic reflection coefficients （σ） were measured, and changes in filamentous actin （F -actin） measured by F-actin fluorometry, and expression of nitrotyrosine analyzed by immunocytochemistry were observed in cultured HUVECs. Results Compared with the control group, the LPS alone group Kf values were significantly increased and the σ values decreased, the F-actin content was decreased and the expression of nitrotyrosine was increased （all P〈0.01）, especially in the high dose LPS alone group. The co-treatment of propofol and LPS significantly reduced levels of LPS -enhanced nitrotyrosine protein, and significantly attenuated the changes in Kf and σ values （all P〈0.01）, while introlipid group had no such benefical effects. Conclusion Propofol rather than introlipid, significantly inhibit LPS -induced increase in permeability of HUVECs and alterations in F-actin organization. The scavenging actions of propofol on peroxynitrite may be helpful to attenuate endothelial barrier dysfunction as shown in our current study.

关 键 词：丙泊酚 脂多糖 内皮细胞 细胞骨架 通透性 

分 类 号：R686[医药卫生—骨科学]