辛伐他汀对同型半胱氨酸诱导的人脐静脉内皮细胞的毒性和炎症反应的影响

目的探讨辛伐他汀对同型半胱氨酸(homocysteine,HCY)诱导的内皮细胞毒性和炎症的抑制作用。方法用不同浓度的HCY(0．1、0．25、0．5、1 mmol／L)处理人脐静脉内皮细胞24 h,采用四氮唑蓝检测细胞存活率;辛伐他汀(1、10、20μmol／L)预处理人脐静脉内皮细胞1 h,然后与HCY(0．25 mmol／L)共孵育,采用MTT检测细胞存活率,Western印迹和ELISA分析不同时间点相关炎性因子蛋白的表达。结果HCY处理后,人脐静脉内皮细胞存活率显著降低;而经过辛伐他汀(1、10、20μmol／L)预处理后,内皮细胞活性分别为47％±4％、68％±6％、89％±6％,明显高于单纯HCY(0．25 mmol／L)处理组(22％±3％,P均<0．01)。由HCY诱导的内皮细胞TNF-α、IL-6、MCP-1及ICAM-1的表达分别为0．23±0．05、0．14±0．03、0．13±0．04、0．21±0．07,与0 h时比较差异无统计学意义。结论辛伐他汀对同型半胱氨酸介导的内皮细胞损伤及炎症反应有明显的抑制作用。

Effects of simvastatin on homocysteine-induced endothelial dysfunction and inflammatory response

OBJECTIVE: To investigate the effects of simvastatin (SIM) on homocysteine (HCY)-induced endothelial dysfunction and inflammatory response. METHODS: Human umbilical vein endothelial cells (HUVECs) were isolated from the umbilical cords from healthy lying-in women and cultured and added with HCY of the concentrations of 0.1, 0.25, 0.5, and 1 mmol/L respectively, or HCY 0.25 mmol/L + SIM of the concentrations of 1, 10 and 20 micromol/L respectively for 1 hour. ELISA was used to detect the cell viability with MTT method. Western blotting was used to examine the protein expression of the cell inflammatory factors, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, macrophage chemoattractant protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1, ELISA was used to detect the contents of the cell inflammatory factors. RESULTS: HCY of different doses inhibited the viability of HUVECs dose-dependently (all P < 0. 01). The survival rates of the HCY-induced HUVECs pretreatment by SIM of the concentrations of 1, 10 and 20 micromol/L for 1 hour were 1.72 +/- 0.03 times, 2.54 +/- 0.09 times, and 3.14 +/- 0.11 times respectively that of the control group (all P < 0. 01). HCY of different concentration of 0.25 mmol/L increased the protein expression of TNF-alpha, IL-6, MCP-1, and ICAM-1 significantly; however, the expression levels of TNF-alpha, IL-6, MCP-1, and ICAM-1 of the 0.25 mmol/L HCY-treated HUVECs that were pretreated by SIM of the concentration of 10 micromol/L for 1 hour were, 0.23 +/- 0.05, 0.14 +/- 0.03, 0.13 +/- 0.04, and 0.21 +/- 0.07 respectively, not significantly different from those at the time of 0 hour (all P > 0.05). CONCLUSION: Simvastatin inhibits the homocysteine-induced endothelial impairment and inflammatory response.