诱导型一氧化氮合酶基因敲除小鼠的心肌缺血/再灌注损伤

Myocardial ischemia/reperfusion injury in the inducible nitric oxide synthase knockout mice.

作者信息

Xi L, Jarrett N C, Hess M L, Kukreja R C

机构信息

Division of Cardiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.

出版信息

Life Sci. 1999;65(9):935-45. doi: 10.1016/s0024-3205(99)00323-9.

DOI:10.1016/s0024-3205(99)00323-9

PMID:10465353

Abstract

Inducible nitric oxide synthase (iNOS) plays an important role in the inflammatory process of certain major cardiac disorders including myocardial infarction and allograft rejection. However, the role of iNOS in acute myocardial ischemia has not been well defined. We determined the effects of genetically disruption of the intact iNOS system on cardiac tolerance to ischemia/reperfusion injury. Adult male wild-type (WT) and iNOS knockout (KO) B6,129 mice were subjected to 20 min global ischemia and 30 min reperfusion in a Langendorff isolated perfused heart model (37 degrees C, n = 10/each group). Ventricular contractile function, heart rate, coronary flow, and leakage of intracellular enzymes (CK and LDH) were not significantly different between the groups during pre-ischemia as well as reperfusion period (P > 0.05). Myocardial infarct size was also not significantly different between WT (20.2+/-2.0% of risk area) and KO mice (23.5+/-3.8%; Mean+/-SEM, P > 0.05). However, the post-ischemic heart rate was significantly preserved in KO as compared to WT (P < 0.05). We conclude that disruption of iNOS gene does not exacerbate ischemia/ reperfusion injury in the heart.

摘要

诱导型一氧化氮合酶（iNOS）在某些主要心脏疾病（包括心肌梗死和同种异体移植排斥反应）的炎症过程中起重要作用。然而，iNOS在急性心肌缺血中的作用尚未明确。我们确定了完整的iNOS系统基因破坏对心脏对缺血/再灌注损伤耐受性的影响。成年雄性野生型（WT）和iNOS基因敲除（KO）的B6,129小鼠在Langendorff离体灌注心脏模型（37℃，每组n = 10）中经历20分钟全心缺血和30分钟再灌注。在缺血前以及再灌注期间，两组之间的心室收缩功能、心率、冠状动脉血流量和细胞内酶（CK和LDH）泄漏无显著差异（P> 0.05）。WT小鼠（梗死面积占危险区的20.2±2.0%）和KO小鼠（23.5±3.8%；平均值±标准误，P> 0.05）之间的心肌梗死面积也无显著差异。然而，与WT小鼠相比，KO小鼠缺血后的心率得到了显著保留（P < 0.05）。我们得出结论，iNOS基因的破坏不会加重心脏的缺血/再灌注损伤。