Immunological regulation of multiple organ failure by reperfusion injury.

心肌缺血后再灌注损伤是通过在缺血心脏内重建冠脉循环而造成的。为了分析再灌注损伤的发病机制，制定治疗措施，我们采用Ono和Lindsey方法建立了异位移植模型。缺血60min后，心肌组织再灌流，中性粒细胞与内皮细胞黏附强烈。此外，心肌间质出血、炎症、心肌三磷酸腺苷含量降低、心肌变性导致心肌收缩终止。给予单抗R2-1A6可显著抑制中性粒细胞与内皮细胞的结合、随后的炎症反应和心肌变性。建立血液灌流大鼠离体心模型(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。观察再灌流后细胞因子基因表达和左心功能的变化。虽然中性粒细胞介导的炎症和心肌变性不明显，但再灌流后心功能明显恶化。此外，IL-1α在缺血心脏再灌流时被特异性检测到，提示IL-1α等细胞因子可能直接参与了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.