洛伐他汀抑制人脐静脉内皮细胞基质金属蛋白酶9表达和活性

Lovastatin Inhibits Matrix Metalloproteinase-9 Expression and Activity of Human Umbilical Vein Endothelial Cells

目的观察洛伐他汀对人脐静脉内皮细胞基质金属蛋白酶9表达的影响。方法体外培养人脐静脉内皮细胞,加入20μg/L肿瘤坏死因子α诱导后,再用0.05～1.35μmol/L洛伐他汀处理0～24 h,蛋白印迹以及逆转录聚合酶链反应分别检测基质金属蛋白酶9的蛋白和mRNA表达情况,明胶酶谱法测定基质金属蛋白酶9活性。结果肿瘤坏死因子α能诱导人脐静脉内皮细胞的基质金属蛋白酶9表达和活性增强,洛伐他汀处理后,基质金属蛋白酶9的mRNA水平、蛋白量及活性均降低,且呈明显的时间和剂量依赖性,其中0.05μmol/L洛伐他汀能显著降低基质金属蛋白酶9的mRNA水平,但在蛋白水平和基质金属蛋白酶9活性上,0.05μmol/L洛伐他汀并没有表现出显著的降低效果,其余洛伐他汀各浓度均能对基质金属蛋白酶9的mRNA水平、蛋白量及活性产生显著的抑制作用,以1.35μmol/L洛伐他汀的抑制效果最显著。结论洛伐他汀能抑制肿瘤坏死因子α诱导的人脐静脉内皮细胞基质金属蛋白酶9的表达。

Aim To study the effect of lovastatin on expression and activity of matrix metalloproteinase-9（MMP-9） in a human umbilical vein endothelial cells（HUVECs） line.Methods Cultured HUVECs were stimulated by 20 μg/L tumor necrosis factor-alpha（TNF-α）,and then incubated with 0.05-1.35 μmol/L of lovastatin for 0-24 h.The protein and mRNA level were detected by Western blotting and reverse transcription polymerase chain reaction（RT-PCR） respectively,and the activity of MMP-9 was analyzed by gelatin zymography.Results MMP-9 expression was induced by TNF-α in HUVECs,lovastatin attenuated both expression and activity of MMP-9 in a time and dose-dependent manner.0.05 μmol/L lovastatin inhibited MMP-9 expression in mRNA level,but not in protein level,but activity of MMP-9 cannot be inhibited by 0.05 μmol/L lovastatin.Other concentration of lovastatin groups can inhibit MMP-9 expression both in mRNA and protein levels,including activity of MMP-9,the maximum inhibitory effect was induced by 1.35 μmol/L lovastatin.Conclusion Expression and activity of MMP-9 can be inhibited by lovastatin in HUVECs.