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

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。

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

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 MMP1 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~(-5)mmol/L) were also respectively determined by the same method after 6、24 and 48 hours.Results Atrovastatin inhi-(bited) the secretion of MMP-1in 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.