中文摘要：

目的研究丁酸钠对缺氧血管内皮细胞通透性改变的影响及其机制。方法人脐静脉内皮细胞（Human umbelical vein endothelial cells,HUVECs）分为常氧组（21%O2）、缺氧组（1%O2）及缺氧＋丁酸钠组（n=3）,缺氧＋丁酸钠组分为0、0.3、1、3 mmol/L 4个剂量组（n=3）。利用三气培养箱模拟缺氧环境,将缺氧组及缺氧＋丁酸钠组置于箱内培养,常氧组置于普通培养箱中培养;利用Transwell小室检测HUVECs单层通透性;Western blot检测黏附连接相关蛋白p120、β-catenin蛋白表达;免疫荧光检测技术观察p120、β-catenin的表达和分布。结果缺氧组HUVECs单层通透性较常氧组增加,差异具有统计学意义（16%vs 10%,P〈0.05）;在丁酸钠（1 mmol/L）作用下,缺氧所致的单层通透性增加被抑制,与缺氧组比较差异具有统计学意义（P〈0.05）。与常氧组比较,缺氧组培养12 h,内皮细胞p120蛋白表达降低,差异具有统计学意义（P〈0.05）,而缺氧对β-catenin蛋白表达没有明显影响;缺氧＋丁酸钠（1 mmol/L）组与缺氧组比较,p120蛋白水平增加,差异具有统计学意义（P〈0.05）。另外,免疫荧光数据显示：缺氧导致p120荧光强度降低,而复合1 mmol/L丁酸钠,p120蛋白荧光强度增高。结论在缺氧引起的血管内皮细胞高通透性的模型中,丁酸钠可能通过升高p120蛋白表达,抑制内皮细胞间黏附连接的破坏,从而维持缺氧血管内皮完整,抑制缺氧血管内皮通透性的增加。

英文摘要：

Objective To determine the effect of sodium butyrate （NaB） on the permeability of vascular endothelial cells induced by hypoxia and investigate its underlying mechanism. Methods Human umbelical vein endothelial cells （HUVECs） were divided into normoxic group （21% O2 ）, hypoxia group （ 1% O2 ） and hypoxia plus NaB treatment groups （0, 0.3, 1 and 3 mmol/L, n = 3 ）. A three-gas incubator was used to contain the cells of hypoxia groups, and the cells of normoxic group were cultured in normoxic incubator. The monolayer permeability of HUVECs was tested by Transwell chamber test. Western blotting was performed to detect the protein expression of p120 and β-catenin. The fluorescence intensities of protein p120 and β-catenin were observed by immunofluorescence assay. Results The monolayer permeability of HUVECs was significantly higher in the hypoxia groups than the normoxic group （ 16% vs 10%, P 〈 0.05 ）. After addition of 1 mmol/L NaB, the increased monolayer permeability of hypoxia group was inhibited significantly （P 〈 0.05 ）. Hypoxia treatment for 12 h induced the protein level of p120 reduced, significantly lower than that of the normoxic group （P 〈 0.05 ）, but hypoxia had no obvious effect on the expression of β-catenin. Hypoxia plus 1 mmol/L NaB treatment promoted the expression of p120 when compared with the simple hypoxia group （ P 〈 0.05 ）. Immunofluorescence assay showed that the fluorescence intensity of p120 was reduced by hypoxia, but 1 mmol/L NaB reversed this phenomenon. Conclusion NaB prevents the hyperpermeability of HUVECs induced by hypoxia, which may be through upregulating p120 protein and thus inhibiting the destruction of the cell adhesion. Therefore NaB inhibits the increase of the permeability of endothelial cells induced by hypoxia.