Kanno Yoshinori, Watanabe Ryo, Zempo Hirofumi, Ogawa Masahito, Suzuki Jun-Ichi, Isobe Mitsuaki
Department of Cardiovascular Medicine, Tokyo Medical and Dental Universit, Japan.
Int Heart J. 2013;54(3):176-80. doi: 10.1536/ihj.54.176.
Chlorogenic acid (CGA), which is a key component of coffee, has many biological effects such as anti-inflammation activity. However, the effects of CGA on ventricular remodeling after myocardial ischemia have not been well investigated. To test the hypothesis that CGA can attenuate chronic ventricular remodeling after myocardial ischemia, we orally administered CGA to murine myocardial ischemia models. Seven to nine week-old C57BL/6 mice were used. A myocardial infarction (MI) model was produced by permanent ligation of the left anterior descending coronary artery (LAD) using an 8-0 suture passed under the arteries. These mice were randomly assigned into 4 groups in each experimental model. Some MI mice were supplemented orally with CGA (30 mg/kg/day, MI+CGA group, n = 13) as a CGAtreated MI group, and other MI mice received vehicle (MI+vehicle group, n = 11) as a vehicle-treated MI group. Shamoperated mice without MI also received vehicle (Sham+vehicle group, n = 3) as a sham group, and sham-operated mice without MI received CGA (30 mg/kg/day, Sham+CGA group, n = 8) as a Sham+CGA group. Just before sacrifice on day 14, we measured blood pressure and heart rate and performed echocardiography. We obtained 3 transverse sections per heart for histopathologic examination. There were no differences in body weight, heart rate, or blood pressure among the groups on day 14. The vehicle-treated MI group showed significantly impaired left ventricular contraction compared to the sham-operated group. However, the CGA-treated MI group showed significantly improved ventricular contraction compared to the vehicle-treated MI group. Severe myocardial fibrosis with enhanced macrophage infiltration was observed in the vehicle-treated ischemia group on day 14. CGA attenuated these fibrotic changes with suppressed macrophage infiltration without systemic adverse effects. CGA may effectively suppress chronic ventricular remodeling after myocardial ischemia because it is critically involved in the suppression of macrophage infiltration.
绿原酸（CGA）是咖啡的关键成分，具有多种生物学效应，如抗炎活性。然而，CGA对心肌缺血后心室重构的影响尚未得到充分研究。为了验证CGA可减轻心肌缺血后慢性心室重构这一假说，我们对小鼠心肌缺血模型口服给予CGA。使用7至9周龄的C57BL/6小鼠。通过用8-0缝线在动脉下方穿过永久性结扎左冠状动脉前降支（LAD）制备心肌梗死（MI）模型。在每个实验模型中，这些小鼠被随机分为4组。一些MI小鼠口服补充CGA（30mg/kg/天，MI + CGA组，n = 13）作为CGA治疗的MI组，其他MI小鼠接受载体（MI +载体组，n = 11）作为载体治疗的MI组。未发生MI的假手术小鼠也接受载体（假手术+载体组，n = 3）作为假手术组，未发生MI的假手术小鼠接受CGA（30mg/kg/天，假手术+ CGA组，n = 8）作为假手术+ CGA组。在第14天处死前，我们测量了血压和心率并进行了超声心动图检查。每颗心脏获取3个横切面用于组织病理学检查。在第14天，各组之间的体重、心率或血压没有差异。与假手术组相比，载体治疗的MI组左心室收缩明显受损。然而，与载体治疗的MI组相比，CGA治疗的MI组心室收缩明显改善。在第14天，在载体治疗的缺血组中观察到严重的心肌纤维化并伴有巨噬细胞浸润增强。CGA减轻了这些纤维化变化，同时抑制了巨噬细胞浸润，且无全身不良反应。CGA可能有效抑制心肌缺血后的慢性心室重构，因为它在抑制巨噬细胞浸润中起关键作用。
