内洋地黄素通过影响细胞凋亡和炎症相关基因表达介导心肌缺血再灌注损伤

目的：利用信号转导基因芯片观察心肌缺血再灌注（myocardial ischemia reperfusion,MIR）时心肌凋亡和炎症相关基因表达变化,以及内洋地黄素特异性拮抗剂地高辛抗体对它们的影响,证明内洋地黄素通过影响细胞凋亡和炎症相关基因表达介导MIR损伤,完善内洋地黄素介导MIR损伤的作用机制。方法：采用结扎大鼠左冠状动脉前降支30min,复灌60min制作在体大鼠MIR模型。SD大鼠随机分成3组,每组3只,分别为假手术组、MIR组、地高辛抗血清组,各组于再灌注60min后立即取左室心尖部缺血区心肌,应用基因芯片技术检测心肌凋亡和炎症相关基因表达。结果：与假手术组比较,MIR组Bax、Bcl-2、Bcl-2L1和Birc1b等凋亡相关基因表达下调,但Bcl-2/Bax比率下降;IL、TNF、ICAM-1等介导炎症相关基因表达有上调或是上调趋势。与MIR组比较,地高辛抗血清组Bax、Bcl-2和Birc3等相关凋亡基因表达均上调,但Bcl-2/Bax比率上升;IL、TNF、ICAM-1等介导炎症相关基因表达下调或是下调趋势。结论：内洋地黄素具有下调抑制凋亡基因表达和上调炎症基因表达作用,内洋地黄素拮抗剂地高辛抗血清通过拮抗内源性洋地黄素,阻断后者的下调抑制心肌凋亡相关基因和上调炎症相关基因表达的作用而发挥心肌保护作用。

Endoxin mediating myocardial ischemia reperfusion injury by effecting expression of apoptosis and inflammation genes

AIM： To observe the changes of cardiac muscle apoptosis and inflammation related gene expression in rats with myocardial ischemia reperfusion （MIR） injury utilizing signal trausduction gene array, and the effects on the rats after injecting antidigoxin, endoxin specificness antagon. It was testified that en- doxin can mediate MIR injury by influencing apoptosis and inflammation related gene, and the mechanism of action of endoxin mediating MIR injury was consummated. METHODS： Myocardial ischemia reperfusion models were obtained by ligating left anterior descending coronary artery 30 minutes, followed by 60 minutes reperfusion. SD rats were randomly divided into three groups each with three rats： sham operation group, MIR group and antidigoxin antiserum group. After reperfusion, left ventricular myocardium samples of ischemia area were immediately processed, and the expression of related apoptosis and inflammation genes were measured with gene array technology. RESULTS： Compared with sham operation group, the apoptosis related gene expression of Bax, Bcl-2, Bcl-2L1 and Birclb in MIR group were down regulated, but the ratio of Bcl-2/ Bax was descended. The mediated inflammation related gene expression of IL, TNF, ICAM-1 were up-regulated or had the tendency of up-regulation. Compared with MIR group, the apoptosis related gene expression of Bax, Bcl-2, Birc3 in antid.igoxin antisenma group were up-regulation, but the ratio of Bcl-2/Bax was upgraded. The mediated inflammation related gene expression of IL, TNF, ICAM-1 were down regulated or had the tendency of down regulation. CONCLUSION： Endoxin can down regulate the inhibition apoptosis gene expression and up-regulate inflammation gene expression. Antagonist of endoxin, antidigoxin antisenma can rivalry endoxin. It has myocardial preservation protection by down regulating the related gene of myocardium apoptosis expression and up-regulating inflammation related gene expression.