一氧化氮对心肌的抑制性保护作用 - 生理学报.pdf

生理学报Acta Physiologica Sinica , June 25, 2011, 63(3): 191–197 191 综 述 一氧化氮对心肌的抑制性保护作用 岳志杰，余志斌* 第四军医大学航空航天生理学教研室，西安 710032 摘 要：内皮型与神经型一氧化氮合酶(eNOS, nNOS)在心肌细胞内持续表达，而细胞应激可引起诱导型NOS (iNOS)表达。心 肌细胞结构型eNOS与nNOS源性NO ，在生理条件下对心肌主要发挥4方面的抑制作用：减缓心肌细胞搏动频率，轻度抑制 心肌细胞收缩功能，加速心肌细胞舒张并增加顺应性，以及轻度抑制线粒体电子传递而增强氧利用效率。在生理条件下动 员心肌储备与心肌肥厚时，与细胞膜上受体形成复合体的eN OS，其分泌的N O通过适度的抑制作用，调和受体介导的信 号，形成类似于增强性拮抗的作用；与RyR形成复合体的nNOS源性NO，经抑制作用而稳定RyR钙释放功能，并增加肌质网 钙离子转运效率。在心肌缺血-再灌注损伤或心力衰竭条件下，除上述eNOS和nNOS源性NO发挥的作用外，iNOS源性NO则 主要通过抑制线粒体的电子传递，防止线粒体可通透转化孔的开放。由上述研究结果可见，无论在生理还是病理条件下， NO呈现出多种适度抑制作用，从而发挥心肌保护作用。 关键词：一氧化氮；心肌保护；抑制 中图分类号：R337.2 Cardioprotection by the inhibitory effect of nitric oxide YUE Zhi-Jie, YU Zhi-Bin* Department of Aerospace Physiology, the Fourth Military Medical University, Xi’an 710032, China Abstract: Endothelial and neuronal nitric oxide synthases (eNOS and nNOS) are constitutively expressed in cardiomyocytes under the physiological condition, while inducible nitric oxide synthase (iNOS) is only expressed in cell stress. Nitric oxide (NO) derived from the constitutive isoforms of eNOS and nNOS plays four kinds of inhibitory effects on the myocardium: reducing the contractile frequency of cardiomyocyte, slightly attenuating cardiac contractility, accelerating relaxation and increasing distensibility of cardio- myocyte, and slightly inhibiting mitochondrial respiration and improving the efficiency of myocardial oxygen consumption. In condi- tions of enhanced cardiac reserve and cardiac hypertrophy, NO derived from eNOS, which forms a complex with a certain kind of re- ceptor on the sarcolemma, modulates receptor-mediated signaling and generates an “accentuated antagonism” by moderate inhibition of cardiac contractility. NO derived from the complex of nNOS-ryanodine receptor (RyR) stabilizes RyR calcium release and increas- es the efficiency of Ca2+ cycling in sarcoplasmic reticulum by the inhibitory effects. However, bes