辛伐他汀对CD40L介导的ECV-304细胞E选择素表达及粘附功能的影响

目的研究在人脐静脉内皮细胞中3-羟-3-甲基戊二酰辅酶A(HMG-CoA)还原酶对CD40/CD40L系统介导的粘附分子表达的影响,及对淋巴细胞与内皮细胞的粘附功能的影响。方法采用人脐静脉内皮细胞株ECV-304,CD40L干预,使之与其表面的CD40作用,用不同浓度辛伐他汀或辛伐他汀(5μmol.L-1)+甲羟戊酸干预,流式细胞术和RT-PCR检测干预前后E选择素(E-Selectin)的表达,流式细胞术检测CD40L介导的淋巴细胞与内皮细胞的粘附功能。结果不同浓度辛伐他汀可下调CD40L介导的E-Selectin的表达,并呈一定的剂量依赖性。甲羟戊酸(400μmol.L-1)抑制了辛伐他汀(5μmol.L-1)对E-Selectin表达的下调作用。辛伐他汀可降低CD40L介导的淋巴细胞与内皮细胞的粘附功能。结论他汀类药物的抗炎作用与抑制CD40-CD40L系统有关,其机制是通过抑制HMG-CoA还原酶而发挥作用的。

Effect of simvastatin on E-Selectin expression and adhesive function assay induced by CD40L in ECV-304 cells

Aim To investigate the effect of the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA)reductase enzyme,simvastatin on E-Selectin ex-pression and adhesive function assay induced by CD40L.Methods Human umbilical vein endothelial cell(HUVEC)was cultured from ECV304 cell strain.Then E-Selectin expression and adhesion of lymphocytes to endothelial cells induced by CD40L and interfered with different concentrations of simvastatin or simvastatin(5 μmol·L-1)+mevalonic acid were determined by RT-PCR and FCM analysis.Results Preincubation of HUVECs with simvastatin(0~10 μmol·L-1)decreased the expression of E-Selectin induced by CD40L in a concentration-dependent manner.Mevalonic acid(400 μmol·L-1)inhibited the restrain of simvastatin on E-Selectin expression.Moreover,preincubation with simvastatin,decreased significantly adhesion of lymphocytes to endothelial cells induced by CD40L.Conclusions Simvastatin inhibits activation of endothelial cells induced by the CD40L/CD40 pathway through HMG-CoA dependent effect.