辛伐他汀含药血清对U937单核巨噬细胞MMP-9及TIMP-1表达与分泌的影响  

Effects of Simvastatin Drug-serum on Expression and Secretion of MMP-9 and TIMP-1 in U937 Monocyte-derived Macrophages

作　　者：刘金来[1] 朱强锋[1] 郝宝顺[1] 

机构地区：[1]中山大学附属第三医院心内科,广东广州510630

出　　处：《中山大学学报（医学科学版）》2007年第5期501-505,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金(07001556)

摘　　要：【目的】探讨辛伐他汀含药血清对U937单核细胞源巨噬细胞基质金属蛋白酶-9(MMP-9)及金属蛋白酶组织抑制因子-1(TIMP-1)表达与分泌的影响。【方法】15只新西兰大白兔随机分为正常对照组(NL,n=5)、粥样硬化模型组(AS,n=5)和辛伐他汀含药血清组(SIM,n=5)。通过喂养高脂饲料,建立兔动脉粥样硬化模型后,予辛伐他汀药液灌胃,获得含药血清。分别予不同浓度含药血清(5%、10%、20%)培养U937单核细胞源巨噬细胞24 h,应用逆转录聚合酶链反应检测MMP-9 mRNA及TIMP-1 mRNA的表达,以及应用酶联免疫吸附试验检测MMP-9及TIMP-1蛋白的分泌。【结果】与相同浓度AS组比较,5%、10%、20%SIM组U937单核细胞源巨噬细胞MMP-9 mRNA表达均显著性降低(P值为0.005、0.041和0.013);5%、10%、20%SIM组TIMP-1 mRNA表达无显著性差异(P值均>0.05)。而与相同浓度AS组比较,不仅10%、20%SIM组MMP-9分泌显著性减少(P值分别为0.009和0.001),而且10%、20%SIM组TIMP-1分泌均显著性增加(P值分别为0.017和0.001)。【结论】辛伐他汀可抑制单核巨噬细胞MMP-9的表达和分泌,以及促进TIMP-1的分泌。[Objective] To investigate the effects of simvastatin drug-serum on the expression and secretion of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in U937 monocyte-derived macrophages. [ Methods] Fifteen New Zealand rabbits were randomized to 3 groups, normal control group （NL, n=5）, atherosclerotic model group （AS, n=5） and simvastatin drug-serum group （SIM, n =5）. The rabbit atherosclerotic model was developed by high cholesterol feeding. Then they were medicated with simvastatin liquor by garage to prepare simvastatin drug-serum. U937 monocyte-derived macrophages were incubated with different concentrations （5%, 10%, and 20%） of simvastatin drug-serum for 24 hours. The mRNA expression and protein secretion of MMP-9 and TIMP-1 were detected by RT-PCR and ELISA. [Results] Compared to same concentration AS group, 5%, 10%, and 20% SIM group significantly inhibited the expression of MMP-9 mRNA in U937 monocyte-derived macrophages （P=0.005, 0.041, and 0.013）, and the expression difference of TIMP-1 mRNA were not significant （all P 〉0.05）. Compared to same concentration AS group, 10% and 20% SIM group not only significantly inhibited the secretion of MMP-9 in U937 monocyte-derived macrophages （P=0,009 and 0,001）, but also significantly increased the secretion of TIMP-1 （ P = 0.017 and 0.001） , [Conclusion] Simvastatin inhibits the expression and secretion of MMP-9 and enhances the secretion of TIMP-1.

关 键 词：辛伐他汀 巨噬细胞 基质金属蛋白酶-9 金属蛋白酶组织抑制因子-1 

分 类 号：R972[医药卫生—药品] Q786[医药卫生—药学]