Effect of prazosin on MMP-1 and TIMP-1 expression in atherosclerosis plaque of ApoE -/- mice model / 重庆医学

ABSTRACT

Objective To observe the effects of prazosin on matrix metalloproteinase‐1(MMP‐1) and tissue inhibitor of met‐alloproteinase 1 (TIMP‐1) expression in atherosclerosis plaque of ApoE knock‐out(ApoE-/- ) mice model and to explore its anti‐atherosclerotic effect and mechanism .Methods Twenty‐four 8‐week‐old ApoE-/- mice were randomly divided into the normal diet group ,high‐fat diet group and prazosin group ,8 cases in each group .The normal diet group was fed by common fodder ,while the high fat group and prazosin group were fed by high fat diet ;on the basis of the high fat diet ,the prazosin group was started to con‐duct gavage of prazosin hydrochloride 1 mg/kg every day ,while the normal diet group and the high fat diet group were daily ga‐vaged by the same volume of normal saline .The abdominal aortic venous blood after 12 weeks in each group was collected for detec‐ting the blood lipid levels .The aorta arterial blood sample was collected for detecting MMP‐1 and TIMP‐1 expression levels by im‐munohistochemistry .Results Compared with the high fat diet group ,the levels of serum TG ,TC and LDL‐C in the prazosin group were significantly decreased ,and the HDL‐C level was increased ,the differences were statistically significant (P< 0 .01 or P<0 .05);the area of aorta arterial atherosclerotic plaque and intima thickness were significantly increased ,while prazosin could signif‐icantly inhibit the plaque formation and intima hyperplasia ;compared with the normal diet group ,the expression level of MMP‐1 protein in the high fat diet group and prazosin group was significantly increased ,while the TIMP‐1 protein expression level was de‐creased ,moreover the MMP‐1 protein expression level in the prazosin group was lower than that in the high fat diet group ,while the TIMP‐1 protein expression level was higher than that in the high fat diet group ,the differences were statistically significant (P<0 .05) .Conclusion Prazosin can decrease the level of TC and LDL‐C ,increase the HDL‐C level and has certain anti‐atherosclerotic effect ,its mechanism may be related with the decrease of the MMP‐1 level and the increase of the TIMP‐1 level in plaque .