Immunological regulation of multiple organ failure by reperfusion injury.

心脏缺血再灌注损伤是通过冠状动脉循环重建引起的。为了探讨再灌注损伤的发病机制，建立治疗方法，我们采用Ono和Lindsey方法建立了大鼠异位移植模型。缺血60 min后再灌注心肌组织中中性粒细胞与内皮细胞的粘附增强。此外，还出现间质出血、炎症、心肌ATP减少、心肌变性，导致心肌收缩终止。单克隆抗体R2- 1A 6的施用显著抑制中性粒细胞与内皮的结合，随后的炎症和心肌变性。建立了大鼠离体心脏血液灌流模型（Langendorff模型）。在这个模型中，我们可以分析缺血心脏在再灌注损伤中的功能方面。观察再灌注后细胞因子基因表达与左室功能的关系。再灌注后，心肌细胞炎症反应和心肌细胞变性不明显，但心室功能明显恶化。此外，IL-1 α在缺血心脏再灌注时特异性检测到，表明IL-1 α等细胞因子可能直接参与再灌注损伤的发病机制。

The post-ischemic reperfusion injury of hearts was induced by re-establshment of coronary circulation into ischemic hearts. In order to analyze the pathogenesis of reperfusion injury and establish therapeutic means, we established a heterotopic transplantation model by Ono and Lindsey method. After 60 min ischemia, the reperfusion of cardiac tissue resulted in strong adhesion of neutrophils to endothelium. In addition, intersitial hemorrhage, inflammation, decrease of myocardial ATP,and myocardial degeneration occured with resulted in termination of myocardial contraction. Administration of monoclonal antibody, R2-1A6 significantly inhibited the binding of neutrophils to endothelium, subsequent inflammation and myocardial degeneration. We also established blood perfused isolated rat heart model (Langendorff model). In this model, we can analyze the functional aspect of ischemic hearts in reperfusion injury. Cytokine gene expression and left ventricular function after reperfusion were studied. Although neutrophil-mediated inflammation and myocardial degeneration was not obvious, the deterioration of ventricle function wea evident after reperfusion. In addition, IL-1alpha was specifically detected upon reperfusion of ischemic hearts, indicating that cytokines such as IL-1alpha may be directly involved in pathogenesis of reperfusion injury.