基质金属蛋白酶在心肌肥厚大鼠中的作用及强力霉素的干预效果

目的:观察心肌肥厚大鼠模型中基质金属蛋白酶(MMP)-2,MMP-9及其抑制剂(TIMP-1)的表达及强力霉素干预后对其影响。方法:24只大鼠随机分为对照组(A组,只给予0.9%氯化钠溶液腹腔注射);造模组(B组)和药物干预组(C组)均用去甲肾上腺素1.06mg/kg腹腔注射,bid,注射15d,建立大鼠心肌肥厚模型,C组造模同时给予强力霉素10mg/kg腹腔注射,qd,给药15d。全部动物于给药后16d处死测定全心质量指数、左室质量指数、心肌胶原含量、心肌组织MMP-2,MMP-9,TIMP-1、心肌胶原容积分数(CVF)。结果:与A组比较,B组全心质量指数、左室质量指数、MMP-2、MMP-9阳性表达率、心肌胶原含量及CVF均明显增加(P<0.05),TIMP-1阳性表达率明显降低(P<0.05)。与B组比较,C组全心质量指数、左室质量指数、MMP-2、MMP-9阳性表达率、心肌胶原含量及CVF均明显降低(P<0.05),TIMP-1阳性表达率增加(P<0.05)。结论:去甲肾上腺素诱导的心肌肥厚大鼠MMPs/TIMPs系统平衡破坏,使基质胶原降解与合成平衡破坏,从而导致心室重构。强力霉素可通过抑制MMP来逆转心室重构。

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(P<0.05),Wherease the expression of TIMP-1 were markedly reduced(P<0.05).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(P<0.05).The expression of TIMP-1 markedly enhanced(P<0.05).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.