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摘要：
目的 探讨不同浓度丙泊酚对人脐静脉内皮细胞（human umbilical vein endothelial cell, HUVEC）活力、内皮损伤相关蛋白［可溶性血栓调节蛋白（soluble thrombomodulin, sTM）、内皮细胞特异性分子‑1（endothelial cell specific molecule‑1, ESM‑1）、E‑选择素（E‑selectin, CD62E）］、内皮细胞紧密连接蛋白［咬合蛋白（occludin）、闭锁连接蛋白‑1（zonula occludens 1, ZO1）、闭合蛋白（claudin 5）］和血管内皮生长因子（vascular endothelial growth factor, VEGF）表达的影响。 方法 以体外培养的HUVEC 3~5代作为实验对象。细胞分入：A组，细胞正常培养组；B组，100 μmol/L丙泊酚组；C组，1 000 μmol/L丙泊酚组；D组，和1 000 μmol/L丙泊酚同等剂量的中/长链脂肪乳剂组；各组处理细胞24 h。3‑（4，5‑二甲基噻唑‑2）‑2，5‑二苯基四氮唑溴盐（噻唑蓝）［3‑（4,5‑dimethyl‑2‑thiazolyl）‑2,5‑diphenyl‑2‑H‑tetrazolium bromide, MTT］比色法检测细胞活力，Western blot检测sTM、ESM‑1、CD62E、occludin、ZO1、claudin 5和VEGF在内皮细胞模型中的表达情况。 结果 与A组比较，C组细胞活力明显降低（P<0.05），B组、D组差异无统计学意义（P>0.05）。与A组比较，C组sTM的表达明显升高（P<0.05），B组、D组sTM表达差异无统计学意义（P>0.05）。与A组比较，B组、C组、D组ESM‑1和CD62E表达差异无统计学意义（P>0.05）。与A组比较，C组occludin的表达明显降低（P<0.05），B组、D组occludin的表达差异无统计学意义（P>0.05）。与A组比较，B组、C组、D组claudin‑5和ZO1表达差异无统计学意义（P>0.05）。与A组比较，B组、C组VEGF的表达明显升高（P<0.05），D组VEGF表达差异无统计学意义（P>0.05）。 结论 高浓度丙泊酚通过调节sTM和occludin的表达导致血管内皮细胞通透性升高，并且VEGF信号通路参与了药物诱导内皮细胞通透性增高。
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Abstract: Objective To investigate the effect of different concentrations of propofol on the viability of human umbilical vein endothelial cell (HUVEC), endothelial damage related proteins ［soluble thrombomodulin (sTM), endothelial cell specific molecule‑1 (ESM‑1), E‑selectin (CD62E)］, endothelial cell tight junction proteins ［occludin, zonula occludens 1 (ZO1), claudin 5］ and vascular endothelial growth factor (VEGF). Methods HUVEC (3−5 passages) were cultured in vitro. The cells were divided into four groups: group A (the cells were normally cultivated); group B, a 100 μmol/L propofol group; group C, a 1 000 μmol/L propofol group; group D, a medium/long chain fat emulsion group with the same dose of 1 000 μmol/L propofol. Each group was treated for 24 h. The cell viability was determined by 3‑（4,5‑dimethyl‑2‑thiazolyl）‑2,5‑diphenyl‑2‑H‑tetrazolium bromide (MTT) assay. Meanwhile, the expression of sTM, ESM‑1, CD62E, occludin, ZO1, claudin‑5 and VEGF in the endothelial cells were measured by Western blot. Results Compared with group A, cells in group C showed remarkably reduced viability (P<0.05), without significant changes in groups B and D (P>0.05). Compared with group A, the expression of sTM in group C remarkably increased (P<0.05), without significant changes in groups B and D (P>0.05). Compared with group A, there was no statistical difference in the expression of ESM‑1 and CD62E protein in groups B, C and D (P>0.05). Compared with group A, the expression of occludin in group C remarkably decreased (P<0.05), without significant changes in group B and group D (P>0.05). Compared with group A, there was no statistical difference in the expression of claudin‑5 and ZO1 in groups B, C and D (P>0.05). Compared with group A, the expression of VEGF protein in group B and group C remarkably increased (P<0.05), without significant changes in group D (P>0.05). Conclusions A high concentration of propofol can increase the permeability of vascular endothelial cells by regulating the expression of sTM and occludin, and the VEGF signaling pathway is involved in drug‑induced increases in endothelial cell permeability.
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