新型他汀类药物——ZD4522对ApoE基因敲除小鼠血管内皮粘附功能的影响

Effect of ZD4522,a new drug of statins,on the adhesive attraction of vascular endothelia in ApoE-knockout mice

目的 :观察他汀类新药ZD45 2 2对ApoE基因敲除小鼠主动脉内皮粘附单核细胞的抑制效应。 方法 :40只高胆固醇血症动物模型 ApoE基因敲除小鼠随机均分为A ,B ,C ,D ,E 5组 ,各组ZD45 2 2的皮下注射剂量分别为 0 ,1,5 ,2 0和 2 0mg·kg-1,qd ,E组给药 6周 ,其余 4组均给药 2周。 2或 6周后测定小鼠血浆胆固醇水平和主动脉内皮对单核细胞的粘附率。结果 :5组ApoE基因敲除小鼠血浆胆固醇水平均比正常小鼠显著升高 (P <0 .0 1) ,与A组比较 ,E组血浆胆固醇水平明显降低 (P <0 .0 1)。 5组ApoE基因敲除小鼠的主动脉内皮单核细胞粘附率均高于正常组 ,与A组比较 ,C ,D ,E组的单核细胞粘附率均显著降低 (P <0 .0 5 ,P <0 .0 1,P <0 .0 1)。结论 :他汀类新药ZD45 2 2对ApoE基因敲除小鼠血管内皮粘附单核细胞有明显的抑制作用 。

Objective:To observe the inhibitory effect of ZD4522 on the adhesion of vascular endothelia to monocytes in AopE knockout mice. Methods:40 ApoE knockout mice were randomly and equally divided into group A,B,C,D and E and to receive 0,1,5,and 20 mg·kg -1 ZD4522 for 2 weeks in the group A,B,C and D.The group E was treated with 20 mg·kg -1 ZD4522 for 6 weeks.The plasma cholesterol level and the adhesion of aortic endothelia to monocytes in all groups were measured after 2 or 6 weeks treatment.Results:The plasma cholesterol level was significantly elevated in 5 groups of ApoE knockout mice in comparison with normal mice(玃 <0.01),and the level in group E was markedly lower than that in group A(P<0.01).The endothelial adhesiveness for monocyte in 5 groups were all higher than that in normal group and the adhesion in grup C,D and E were significantly lowere than that in group A( P <0.05, P <0.01, P <0.01).Conclusion:ZD4522 has obvious inhibitory effect on the adhesion of vascular endothelia to monocytes in ApoE knockout mice,and the effect is independent of its lipid lowering effect.