Controlled Release of Matrix Metalloproteinase-1 Plasmid DNA Prevents Left Ventricular Remodeling in Chronic Myocardial Infarction of Rats
Controlled Release of Matrix Metalloproteinase-1 Plasmid DNA Prevents Left Ventricular Remodeling in Chronic Myocardial Infarction of Rats
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DOI：
10.1253/circj.cj-09-0379
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发表时间：
2009-12-01
影响因子：
3.3
通讯作者：
Matsuoka, Satoshi
中科院分区：
文献类型：
--
作者：
Lin, Xue;Jo, Hikari;Matsuoka, Satoshi
背景：本研究探讨缓释基质金属蛋白酶-1 （MMP-1）质粒DNA是否能预防大鼠慢性心肌梗死（MI）模型左心室（LV）重构。方法与结果：将中度心肌梗死大鼠随机分为2组：在梗死周围注射含磷酸缓冲盐水（PBS）微球（MI组，n=14）和注射含MMP-1质粒DNA的阳离子明胶微球（MI+MMP-1组，50 μ g MMP-1/20 μ l, n=14）。作为对照组（n=14），大鼠既不进行冠状动脉结扎，也不注射PBS。进行超声心动图、心导管检查和组织学检查。治疗后2周和4周，心肌梗死+MMP-1组左室舒张末期和收缩末期尺寸均小于心肌梗死组，分数面积变化更好，动力学面积更小。治疗后4周，心肌梗死+MMP-1组左室收缩终弹性和等容舒张时间常数均优于心肌梗死组。心肌梗死+MMP-1组纤维化程度低于心肌梗死组。结论：明胶微球用于MMP-1质粒DNA的控释，有望改善心肌梗死慢性期的心脏重塑和功能。[中国心脏杂志]2009；73:2315-2321。
Background: The present study investigated whether administration of controlled release matrix metalloproteinase-1 (MMP-1) plasmid DNA prevents left ventricular(LV) remodeling in a rat chronic myocardial infarction (MI) model.Methods and Results: Rats with a moderate-sized MI were randomized to 2 groups: injection of phosphate buffered saline (PBS) containing microspheres into the peri-infarct area (MI group, n=14) and injection of cationized gelatin microspheres incorporating MMP-1 plasmid DNA (MI+MMP-1 group, 50 mu g MMP-1/20 mu l; n=14). As a control group (n=14), rats received neither the coronary artery ligation nor the injection of PBS. Echocardiography, cardiac catheterization and histological studies were performed. At 2 and 4 weeks after the treatment, the MI+MMP-1 group had smaller LV end-diastolic and end-systolic dimensions, better fractional area change and smaller akinetic areas than the MI group. The LV end-systolic elastance and time constant of isovolumic relaxation were also better in the MI+MMP-1 group compared with the MI group 4 weeks after the treatment. Fibrosis evaluated with Masson's trichrome staining was less in the MI+MMP-1 group than the MI group.Conclusions: Gelatin microspheres for the controlled release of MMP-1 plasmid DNA are promising for improving cardiac remodeling and function when they are administered during the chronic phase of MI. (Circ J 2009; 73: 2315-2321)