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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。
Objective: To observe the expression of matrix metalloproteinase (MMP) -2, MMP-9 and its inhibitor (TIMP-1) in rat model of cardiac hypertrophy and the effect of doxycycline intervention. Methods: Twenty-four rats were randomly divided into control group (group A, only 0.9% sodium chloride solution injected intraperitoneally); model group (group B) and drug intervention group (group C) were treated with norepinephrine 1.06mg / kg intraperitoneal injection, bid, injection 15d, rat model of myocardial hypertrophy was established. Group C was given intraperitoneal injection of doxycycline 10mg / kg qd for 15 days. Total heart mass index, left ventricular mass index, myocardial collagen content, myocardium MMP-2, MMP-9, TIMP-1, and myocardial collagen volume fraction (CVF) were determined after all the animals were sacrificed on the 16th day after administration. Results: Compared with group A, the levels of total heart mass index, left ventricular mass index, MMP-2 and MMP-9 positive rate, myocardial collagen content and CVF in group B were significantly increased (P <0.05) Significantly lower (P <0.05). Compared with group B, the indexes of cardiac mass index, left ventricular mass index, MMP-2, MMP-9, myocardial collagen content and CVF in group C were significantly lower (P <0.05) and TIMP-1 positive P <0.05). CONCLUSION: The balance of MMPs / TIMPs system in norepinephrine-induced cardiac hypertrophy rats damages the balance of matrix collagen degradation and synthesis, resulting in ventricular remodeling. Doxycycline reverses ventricular remodeling by inhibiting MMPs.