Experimental Study On The Effect Of Statins On Matrix Metalloproteinase-1 (MMP-1) And Matrix Metalloproteinase Tissue Inhibitor-1(TIMP-1) Secreted By Rat Macrophage

Objective: ACS is a series of diseases including instable angina, myocardial infarction, and cardiac sudden death that severely threaten people's health. The use of statins had made a great improvement in reducing the incident rate of ACS and the death rate of ACS. But the mechanism by which the statins prevent atherosclerosis remains unclear. My experimental study is 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 1×10-4 mmol/L to 1×10-7 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 (1×10-5mmol/L) were also respectively determined by the same method after 6,24 and 48 hours.Results: Atrovastatin inhibited the secretion of MMP-1in a time-dose-dependent manner (it decreases the secretion of MMP-1 from 17.36% to 33.70% following the increasing of it's concentration and decreases the secretion of MMP-1 from 11.96% to 32.77% while the contact time last from 6 hours to 48 hours), but does not influence the secretion of TIMP-1. Pravastatin does 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 can not influence the secretion of TIMP-1. In conclusion, it can improve the stability of atherosclerosis plaque. Pravastatin can,t influence the secretion of MMP-1 and TIMP-1.