Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Circ J. 2009 Dec;73(12):2315-21. doi: 10.1253/circj.cj-09-0379. Epub 2009 Oct 2.
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.
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 microg MMP-1/20 microl; 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.
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.
本研究旨在探讨控释基质金属蛋白酶-1（MMP-1）质粒 DNA 能否预防大鼠慢性心肌梗死（MI）模型的左心室重构。
将 MI 大鼠随机分为 2 组：微球包裹的磷酸盐缓冲液（PBS）注射到梗死周边区（MI 组，n=14）和阳离子化明胶微球包裹的 MMP-1 质粒 DNA（MI+MMP-1 组，50μg MMP-1/20μl；n=14）。作为对照组（n=14），大鼠既不接受冠状动脉结扎也不接受 PBS 注射。进行超声心动图、心导管检查和组织学研究。在治疗后 2 周和 4 周时，MI+MMP-1 组的 LV 舒张末期和收缩末期内径较小，分数面积变化较好，无运动区域较小。与 MI 组相比，MI+MMP-1 组的 LV 收缩末期弹性和等容舒张时间常数在治疗后 4 周时也更好。MI+MMP-1 组的 Masson 三色染色评估的纤维化程度低于 MI 组。
在 MI 的慢性期给予 MMP-1 质粒 DNA 控释明胶微球有望改善心脏重构和功能。
