多西环素抑制基质金属蛋白酶对心肌梗死大鼠左室重构和心功能的影响

目的观察多西环素对心肌梗死(myocardial infarc-tion,MI)后大鼠心肌MMP-2和MMP-9活性的影响及其对大鼠心肌梗死后心衰和左室重构的保护作用。方法 48只♂SD大鼠,分为假手术组、模型组、多西环素组,各16只。其中模型组和多西环素组通过结扎冠状动脉左前降支建立MI模型,假手术组仅开胸,未结扎冠状动脉。模型组(腹腔内注射生理盐水0.5 ml,Bid×5 d)、多西环素组(腹腔内注射多西环素15 mg.kg-1.d-1,Bid×5 d),假手术组(腹腔注射生理盐水0.5 ml,Bid×5 d)。术后2周心脏彩超评价心功能,取心肌组织用Masson染色分析心肌梗死面积,明胶酶法分析MMP-2和MMP-9的活性。结果 MI 2周后与模型组相比,多西环素治疗组左室前壁厚度明显增加(P<0.05),左室舒张末期内径缩小(P<0.05),左室短轴缩短率明显增加,EF值增高。治疗组梗死面积百分比缩小,明胶酶谱分析证实治疗组心肌组织MMP-2、MMP-9的活性明显低于模型组。结论多西环素能够在一定程度上通过抑制心肌MMP-2、MMP-9的活性、缩小梗死面积、减轻存活心肌的纤维化而改善心肌梗死大鼠的心功能和左室重构。

Doxycycline attenuates left ventricular remodeling and improves left ventricular function through inhibiting matrix metalloproteinases in post myocardial infarcted rats

Aim To observe the effects of doxycycline on the activity of matrix metalloproteinase-2(MMP-2) and MMP-9,left ventricular remodeling and left ventricular function in the post myocardial infarction(MI) rats.Methods A total of 48 male SD rats were randomly divided into three groups:sham-operated group,model group,doxycycline(DOC) group,with 16 rats in each group.Rats in model group and DOC group were made into models of MI by ligation of anterior descending coronary artery.Rats in DOC group were intraperitoneally injected with doxycycline(15 mg·kg-1·d-1,bid for 5 days),and those in model group were injected with saline solution(0.5 ml bid for 5 days).Rats in sham-operated group undergoing thoracic surgery without ligaturing anterior descending coronary artery were injected with saline solution(0.5 ml bid for 5 days).Cardiac function was evaluated by echocardiography 2 weeks post MI,and the size of MI was analyzed by Masson staining and MMP-2,MMP-9 activity was analyzed by gelatin enzymatic analysis.Results Compared with model group,the left ventricular(LV) wall thickness increased significantly in DOC group,accompanied with the improvement of LV fractional shortening and LV ejection fraction(P<0.05,respectively),while the LV end-diastolic diameter was significantly reduced(P<0.05).Infarct size was reduced significantly in the DOC group(P<0.05).MMP-2,MMP-9 activity in DOC group was significantly decreased than that in the model group.Conclusion Doxycycline improves rat heart function and attenuates left ventricular remodeling of post-MI rats to a certain extent through inhibiting MMP-2,MMP-9 activity,reducing the infarct size,and alleviating myocardial fibrosis of the heart tissues.