Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
Microcirculation. 2013 Jan;20(1):17-29. doi: 10.1111/micc.12002.
The present study was designed to evaluate whether CP was beneficial in alleviating myocardial fibrosis following I/R injury.
Sprague-Dawley rats were subjected to 30 minutes occlusion of the LADCA, followed by reperfusion. CP (0.4 or 0.8 g/kg) was daily administered starting from three hour after reperfusion until day 6. Coronary venular diameter, RBC velocity, albumin leakage, MBF, heart function, myocardial infarction and fibrosis size, myocardium ultrastructure, MPO activity, and MDA level were evaluated. The expression of MCP-1, RP S19, TGF-β1, P-Smad3, Smad4, MMP-9 and α-SMA, and the infiltration of leukocytes were examined.
CP post-treatment ameliorated I/R-induced myocardial RBC velocity reduction, MBF decrease, cardiac dysfunction, and albumin leakage increase. Moreover, myocardial infarction and fibrosis size, MPO activity, MDA level, the expression of RP S19, TGF-β1, P-Smad3, Smad4, MMP-9 and α-SMA, the number of CD68-positive cells increased significantly after I/R, and myocardium collagen deposition was observed on day 6 after reperfusion. All the alterations after I/R were significantly ameliorated by CP.
Post-treatment with CP ameliorates I/R-induced myocardial fibrosis, suggesting that CP may be applied as an option for preventing cardiac remodeling after I/R injury.
本研究旨在评估 CP 是否有益于减轻缺血再灌注损伤后的心肌纤维化。
SD 大鼠结扎左冠状动脉前降支 30 分钟，再灌注。CP（0.4 或 0.8 g/kg）从再灌注后 3 小时开始，每天给药，持续至第 6 天。评估冠状小静脉直径、RBC 速度、白蛋白渗漏、MBF、心功能、心肌梗死和纤维化面积、心肌超微结构、MPO 活性和 MDA 水平。检测 MCP-1、RP S19、TGF-β1、P-Smad3、Smad4、MMP-9 和 α-SMA 的表达以及白细胞浸润情况。
CP 治疗后改善了 I/R 引起的 RBC 速度降低、MBF 降低、心功能障碍和白蛋白渗漏增加。此外，CP 还显著改善了 I/R 后心肌梗死和纤维化面积、MPO 活性、MDA 水平、RP S19、TGF-β1、P-Smad3、Smad4、MMP-9 和 α-SMA 的表达、CD68 阳性细胞数量的增加，以及再灌注后第 6 天的心肌胶原沉积。CP 明显改善了 I/R 后的所有改变。
CP 治疗后可改善 I/R 引起的心肌纤维化，提示 CP 可能作为预防 I/R 损伤后心脏重构的一种选择。
