脂联素对兔短期缺血再灌注心肌的保护作用

Protective Effect of Adiponectin on Short-term Myocardial Ischemia-reperfusion Injury in Rabbits

目的探讨脂联素(adiponectin,APN)对兔短期缺血再灌注损伤心肌的保护作用并探讨其可能机制。方法 18只新西兰大白兔随机分成3组(n=6),假手术对照组(S组)、缺血/再灌注组(IR组)、脂联素组(APN组)。除S组外,其余两组均接受左冠状动脉前降支15 min阻断和30 min再灌注。APN组于再灌注开始时自耳缘静脉注入重组脂联素50μg/kg。检测心肌组织的细胞凋亡情况,血清肿瘤坏死因子α(TNF-α)水平,一氧化氮(NO)含量;免疫组织化学方法检测Bcl-2、Bax蛋白的表达。结果 APN组心肌细胞凋亡指数低于IR组(P<0.01)。APN组Bcl-2基因的蛋白表达量高于IR组(P<0.05),Bax基因的蛋白表达量低于IR组(P<0.05)。APN组血清TNF-α含量低于IR组(P<0.05),NO含量高于IR组(P<0.01)。结论 APN对短期缺血再灌注心肌有一定保护作用,其机制可能与APN增加血清中的NO含量,降低血清中TNF-α水平及上调Bcl-2基因的蛋白表达,下调Bax基因的蛋白表达有关。

Objective To investigate the protective effect of adiponectin on short-term myocardial ischemia-reperfusion injury and the potential mechanism in rabbits.Methods Eighteen rabbits were randomly allocated to three groups（6 in each group）：sham operation group（S group）,ischemia-reperfusion group（IR group）and adiponectin group（APN group）.The rabbits in IR and APN groups were subjected to left anterior descending coronary artery occlusion for 15 min followed by reperfusion for 30 min.In APN group,50 μg/kg adiponectin was injected through ear-border vein within 1 min after ischemia.All animals were killed 30 min after reperfusion for determining the nitric oxide（NO）and tumor necrosis factor-α（TNF-α）in serum.Cardiomyocyte apoptosis was examined by in situ TDT-mediated dUTP nick end labeling（TUNEL）and DNA electrophoresis.The expression of Bcl-2 and Bax proteins was detected by using immunohistochemiscal staining.Results TUNEL detection revealed that the apoptosis index in APN group was obviously lower than that in IR group（P0.01）.The expression of Bcl-2 protein and the concentration of NO in APN group were higher than those in IR group（P0.05 or 0.01）.The expression of Bax protein and the concentration of TNF-α in APN group were lower than those in IR group（P0.05）.Conclusion APN can lower the ratio of apoptosis and protect myocardial cells from IR injury by increasing Bcl-2 expression and decreasing Bax expression.Its mechanism may be involved in the increased concentration of NO and decreased concentration of TNF-α in serum.APN might be potential molecular targets for myocardial IR injury therapy.