脂氧素A4对心肌缺血再灌注损伤的保护作用

目的 探讨脂氧素A4对心肌缺血再灌注损伤的保护作用及可能机制.方法 30只雄性昆明小鼠,随机分为缺血再灌注组(A组),脂氧素A4(LXA4)处理组(B组)和LXA4+ZnPP血红素氧合酶(HO)-1抑制剂]处理组(C组),每组10只.建立小鼠缺血再灌注模型,再灌注30min后各组分别经颈总动脉插管注入同体积的10%无水乙醇、LXA4、LXA4+ZnPP,5 h后测定各组血清中的TNF-α、CK及LDK,心肌组织中髓过氧化物酶(MPO)活性、丙二醛(MDA)含量,TUNEL法检测心肌细胞凋亡率及病理切片观测心肌炎性细胞浸润.结果 与A组比较,B组心肌炎性细胞浸润减少,CK、LDH及MPO活性、TNF-α浓度、NDA含量及心肌凋亡率均显著降低(P<0.01),而ZnPP可以显著减弱LXA4的保护作用(P<0.05).结论 LXA4对心肌缺血再灌注损伤具有保护作用,HO-1可能在LXA4的心肌保护作用中起重要作用.

The protective effects of lipoxin A4 against myocardial ischemia-reperfusion injury

Objective To investigate the roles of lipoxin A4, an endegenous lipid mediator with wide anti-inflammatory fea- tures, in attenuating myocardial ischemia-reperfusion injury and the possible mechanisms. Methods Thirty male KM mice were divid- ed randomly into three groups, 10 in each: ischemia-reperfusion group (group A), lipoxin A4 (0.1 mg/kg) group (group B) and Zn- PP (Zinc protoporphyrin Ⅸ, 25 mg/kg)phus lipoxin A4 (0.1 mg/kg)group (group C). A ischemia-reperfusion heart model was de- veloped by ligating the lift anterior descending branch of the coronary artery. A dine of 10% dehydrated alcohol in 0.2 ml for group A, a dose of isochoric lipoxin A4 for group B and a dose of isochoric ZnPP + lipoxin A4 for group C was infused into the ascending aorta through a catheter, which was kpassing the right common carotid artery, 30 minutes after reperfusion. The concentration of serum TNF-α, activities of serum crestine kinase(CK) and lactate dehydrogenase (LDH), activities of myeloperoxidase (MPO) and malond- ialdehyde (MDA) and the cell apoptosis rate in the myocardial tissue were measured 5 hours after reperfusion. Pathological features of the inflammatory infiltration in the myocardium were also observated.Results As compared with group A, the inflammatoryry infiltra- tion in the ischemic and necrotic regions tithe myocardium was reduced, with group C in the intermediate range. The serum activities of CK and LDH wine significantly lower in group B and C than that in group A, and the lowest activities were detected in group B. Similar findings were observed for MPO, an indicator for neutrophil infiltration, and MDA, an indictor for cell injury caused by oxy- gen radicals, in the myocardium. The concentration of TNF-α and the rate of cadiocyte apoptosis were decreased significantly in group B(P < 0.01). ZnPP, an inhibitor of heine oxygenase (HO)-1, attenusted the above protective effects of lipoxin A4 significantly (P<0.05). Conclusion Lipoxin A4 has protective effects against myocardial ischemia-reperfusion injury, and HO-1 may have a potential role in the protectve mechanisms of lipoxin A4, probably pertly by means of reducing the production of reactive oxygen spe- cies and TNF-α, decreasing the activation and infiltration of neutrophils, alleviating inflammatory damage and avoiding apoptosis.