Role of matrix metalloproteinases in rat cardiac hypertrophy and the effects of doxycycline

Objective:To investigate the expressions of matrix metalloproteinases(MMP-2,MMP-9)and the tissue inhibitor of metalloproteinases(TIMP-1)in norepinephrine-induced rat cardiac hypertrophy and the effects of doxycycline.Method:Twenty-four rats were randomly divided into control group(group A),model group(group B)and drug intervetion group(group C).The rat cardiac hypertrophy models were established by intraperitoneal injection of norepinephrine 1.06mg/kg twice a day for 15 days.The rat cardiac hypertrophy models were established as above in group C and at the same time the rats were provided with doxycycline(10 mg/kg)by intraperitoneal injection once a day for 15 days.All the rats were killed on the sixteenth days.We measured cardia index,left ventricular index and content of collagen,MMP-2,MMP-9 and TIMP-1 in the myocardium as well as collagen volume fraction(CVF).Result:In group A,comparing with the group B,cardia index,left ventricular index,expressions of MMP-2 and MMP-9,content of collagen and CVF were markedly enhanced(P0.05),Wherease the expression of TIMP-1 were markedly reduced(P0.05).In group C,comparing with group B,cardiac index,left ventricular index,the expressions of MMP-2 and MMP-9,the content of collagen and CVF markedly reduced(P0.05).The expression of TIMP-1 markedly enhanced(P0.05).Conclusion:There is a destructive unbanlance in the MMPs/TIMPs systerm in rat cardia hypertrophy induced by norepinephrine.This causes a destructive unbanllance between the degradation and synthesize of the matrix collagen and resultes in ventricular remodeling.Doxycycline can reverse ventricular remodeling by inhibitting the matrix metalloproteinases.