他汀类药物对基质金属蛋白酶-1及组织型基质金属蛋白酶抑制剂-1的影响

Effect of statin on matrix metalloproteinase-1 and matrix metalloproteinase tissue inhibitor-1 secreted by rat macrophage

目的观察阿托伐他汀(立普妥)、普伐他汀(普拉固)对大鼠腹腔巨噬细胞分泌基质金属蛋白酶-1(MMP-1)及组织型基质金属蛋白酶抑制剂-1(TIMP-1)的影响。方法培养的大鼠腹腔巨噬细胞中先加入10ng/ml的白介素-1β(IL-1β),促进MMP-1的分泌,24h后加入不同浓度的阿托伐他汀、普伐他汀(1×10-7mmol/L、1×10-6mmol/L、1×10-5mmol/L、1×10-4mmol/L),继续孵育24h后,采用酶联免疫吸附法(ELISA法)测培养上清液中的MMP-1及TIMP-1的浓度;取阿托伐他汀10-5mmol/L浓度,分别在6h、24h、48h测培养上清液中的MMP-1的浓度。结果随着药物浓度的增加(1×10-7mmol/L、1×10-6mmol/L、1×10-5mmol/L、1×10-4mmol/L),阿托伐他汀对大鼠腹腔巨噬细胞分泌MMP-1的抑制作用逐渐增强(加药组MMP-1分泌较对照组分别减少17.36%、19.40%、26.54%、33.70%),与对照组有显著统计学差异,而不同浓度的普伐他汀虽使大鼠腹腔巨噬细胞分泌MMP-1略有降低,但与对照组比较无统计学差异,且各组间也无统计学差异;两组他汀使大鼠腹腔巨噬细胞TIMP-1的分泌均略有降低,但与对照组比较,均无统计学意义;随着药物作用时间的延长(6h、24h、48h),阿托伐他汀(1×10-5mmol/L)对大鼠腹腔巨噬细胞分泌MMP-1的抑制作用逐渐增强(加药组MMP-1分泌较对照组分别减少11.96%、26.54%、32.77%),与对照组有显著统计学差异。结论阿托伐他汀呈时间剂量依赖性抑制IL-1β介导的大鼠腹腔巨噬细胞分泌MMP-1,而对TIMP-1的分泌无影响;普伐他汀对IL-1β介导的大鼠腹腔巨噬细胞分泌MMP-1无影响,对TIMP-1的分泌也无影响。

Objective To investigate the effect of atrovastatin and pravastatin on matrix metalloproteinase-1 （MMP-1） and matrix metalloproteinase tissue inhibitor-1 （TIMP-1 ） secreted by rat macrophage. Methods Rat peritoneal macrophages were incubated in 24-well plates in serum-free medium with 10ng/ml IL-1β.24 hours later, atovastatin and pravastatin in different concentration （from 1 × 10^-7 mmol/L to 1 × 10^-4 mmol/L） were added to the medium. After 24 hours, supernatant of the medium were collected and MMP-1 and TIMP-1 levels in culture medium were determined with the use of respective ELISA kits according to the manufacturer＇s instructions; MMP-1 levels in culture media with atrovastatin （ 1 ×10^5mnol/L） were also respectively determined by the same method after 6,24 and 48 hours. Results Atrovastatin inhibited the secretion of MMP-lin a time-dose-dependent manner, but did not influence the secretion of TIMP-1. Pravastatin did not influence either the secretion of MMP-1 or the secretion of TIMP-1. Conclusion Atrovastatin can inhibit the secretion of MMP-1 in IL-1β-stimulated macrophage and did not influence the secretion of TIMP-1, so, it can improve the stable of atherosclerosis plaque. Pravastatin can＇t influence the secretion of MMP-1 and TIMP-1.