细胞间粘附分子-1表达水平对心肌再灌注损伤的影响及N-乙酰半胱氨酸的保护作用

Influence of expression of intercellular adhesion molecule-1 on myocardial ischemic reperfusion injury and cardiac protective effect of N-acetylcysteine

目的 探讨细胞间粘附分子 (ICAM 1)表达与中性粒细胞 (PMNs)浸润与心肌缺血再灌注损伤 (IRI)的关系并观察N 乙酰半胱氨酸 (NAC)对IRI的保护效果。方法 大鼠 116只 ,分设 :(1)缺血再灌注 (IR)组 ;(2 )IR +NAC组 ;(3 )假手术对照组 ,并分设再灌注 1、3、6、12、2 4h时相点。取缺血心肌用原位杂交和免疫组织化学检测ICAM 1mRNA及其蛋白表达水平 ,用酶法测定PMNs浸润数 ,TTC染色法测心肌梗死范围。结果 心肌再灌注时 ,ICAM 1表达明显增高 ,其mRNA表达至 6h达高峰 ,而蛋白质表达水平、PMNs浸润数和梗死范围改变于 12～ 2 4h达高峰 ,三者间呈显著正相关 ,但ICAM 1mRNA与后三者间无明显相关性。IR +NAC组上述指标于再灌注时虽也明显增高 ,但比IR组明显减轻 ,除ICAM 1蛋白质表达于再灌注 3h前无显著变化外 ,其余P均 <0 0 5或 0 0 1。结论 心肌IR时 ,ICAM 1参与介导了PMNs对组织细胞的粘附、浸润和IRI的发生、发展 ;NAC可通过抑制ICAM 1的表达而产生心肌保护作用。

Objective To investigate the influence of expression of intercellular adhesion molecule 1(ICAM 1) on myocardial ischemic reperfusion injury (IRI), myocardial infiltration of polymorphonuclear neutrophils(PMNs) and infarction size, and the cardiac protective effect of N acetylcysteine(NAC). Methods One hundred and sixteen rats were divided into three groups: IR, IR+NAC and sham group. The ischemic myocardial samples were studied at 1,3, 6,12, 24 hours after ischemic reperfusion (IR). The levels of expression of ICAM 1 mRNA were evaluated by in situ hybridization and the protein by immunocytochemistry. The numbers of infiltrated PMNs were measured with MPO enzyme marker method and the myocardial infarction area was evaluated by TTC staining method. Results After IR, myocardial levels of expression of ICAM 1 mRNA were increased significantly and reached a peak at 6 h; but the ICAM 1 protein peaked during 12 24 h. Number of PMNs and infarction size also increased and peaked after reperfusion 12 24 h. Close positive correlation ( P <0 05) was found between the levels of expression of ICAM 1 protein, PMNs infarction area of the myocardium. In IR+NAC group, all of the indices were increased after IR, but the levels of increase in IR+NAC group were significantly lower ( P <0.05 or 0 01) as compared with group IR ( P <0 05 0 01). Conclusion The findings indicate that PMNs adhesion and infiltration induced by ICAM 1 is implicated in the development of myocardial IRI. NAC could protect the myocardium from IRI by partially blocking the expression of ICAM 1.