辛伐他汀含药血清对U937单核巨噬细胞MMP-9及TIMP-1表达及分泌.docVIP

辛伐他汀含药血清对U937单核巨噬细胞MMP-9及TIMP-1表达及分泌 　 作者：刘金来, 朱强锋, 郝宝顺 【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 gt;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。 【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 Abstract:【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 gavage 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 gt;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