Fujimoto Hajime, Ohno Minoru, Ayabe Seiji, Kobayashi Hisae, Ishizaka Nobukazu, Kimura Hiroko, Yoshida Ken-ichi, Nagai Ryozo
Department of Cardiovascular Medicine, University of Tokyo, Japan.
Arterioscler Thromb Vasc Biol. 2004 Oct;24(10):1848-53. doi: 10.1161/01.ATV.0000142364.85911.0e. Epub 2004 Aug 12.
Carbon monoxide (CO) is postulated to protect tissues against several types of injuries. We investigated the role of CO in amelioration of cardiac ischemia-reperfusion injury in vivo and the mechanisms involved in it.
Rats inhaled CO (250 ppm, 500 ppm, or 1000 ppm) for 24 hours in a chamber after myocardial ischemia-reperfusion induced by occluding the left anterior descending coronary artery for 30 minutes. Pre-exposure to 1000 ppm of CO significantly reduced the ratio of infarct areas to risk areas and suppressed the migration of macrophages and monocytes into infarct areas, and the expression of tumor necrosis factor (TNF)-alpha in the heart; however, 250 ppm, 500 ppm of CO, or low barometric pressure hypoxia (0.5 atm) did not affect them. Exposure to 1000 ppm CO resulted in the activation of p38 mitogen-activated protein kinase (p38MAPK), protein kinase Balpha(Akt), endothelial nitric oxide synthase (eNOS), and cyclic guanosine monophosphate (cGMP) in the myocardium. Inhibition of p38MAPK, PI3kinase, NO, and soluble guanylate cyclase with SB203580, wortmannin, N(G)-nitro-L-arginine methyl ester (L-NAME), and methylene blue, respectively, attenuated the cytoprotection by CO.
CO has beneficial effects on cardiac ischemia-reperfusion injury; this effect is mediated by p38MAPK pathway and Akt-eNOS pathway, including production of cGMP.
一氧化碳（CO）被认为可保护组织免受多种类型的损伤。我们研究了CO在体内减轻心脏缺血再灌注损伤中的作用及其相关机制。
在通过结扎左前降支冠状动脉30分钟诱导心肌缺血再灌注后，大鼠在舱室内吸入CO（250 ppm、500 ppm或1000 ppm）24小时。预先暴露于1000 ppm的CO可显著降低梗死面积与危险面积的比值，并抑制巨噬细胞和单核细胞向梗死区域的迁移以及心脏中肿瘤坏死因子（TNF）-α的表达；然而，250 ppm、500 ppm的CO或低气压缺氧（0.5 atm）对其无影响。暴露于1000 ppm的CO可导致心肌中p38丝裂原活化蛋白激酶（p38MAPK）、蛋白激酶Bα（Akt）、内皮型一氧化氮合酶（eNOS）和环磷酸鸟苷（cGMP）的激活。分别用SB203580、渥曼青霉素、N（G）-硝基-L-精氨酸甲酯（L-NAME）和亚甲蓝抑制p38MAPK、磷脂酰肌醇3激酶（PI3激酶）、一氧化氮（NO）和可溶性鸟苷酸环化酶，可减弱CO的细胞保护作用。
CO对心脏缺血再灌注损伤具有有益作用；这种作用是由p38MAPK途径和Akt-eNOS途径介导的，包括cGMP的产生。
