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

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (8): 880-885.

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

郑建发, 柯永胜, 高文俊, 汪和贵

皖南医学院心血管疾病研究所、附属弋矶山医院心内科, 芜湖241000, 安徽

收稿日期:2008-04-25 修回日期:2008-07-17 出版日期:2008-08-26 发布日期:2020-10-12
通讯作者: 柯永胜, 男, 教授, 主任医师, 硕士研究生导师, 主要研究方向:心肌缺血再灌注损伤保护与冠心病介入治疗。Tel:0553-5739313　E-mail:keyongsheng@medmail.com.cn
作者简介:郑建发, 男, 医学硕士, 研究方向:心血管药理。现在合肥市第一人民医院心内科。Tel:13866351147　E-mail:zhenjianf a1@163.com

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

ZHENG Jian-fa, KE Yong-sheng, GAO Wen-jun, WANG He-gui

Medical Department of Cardiology of Yijishan Hospital, Cardiovascular Disease Study of Wannan Medical College, Wuhu 241000, Anhui, China

Received:2008-04-25 Revised:2008-07-17 Online:2008-08-26 Published:2020-10-12

摘要/Abstract

摘要： 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30 min, 复灌60 min 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60 min 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。

关键词: 内洋地黄素, 缺血再灌注损伤, 心肌, 基因, 凋亡, 炎症因子

Abstract: AIM:To observe the changes of cardiac muscle apoptosis and inf lammation related gene expression in rats with myocardial ischemia reperfusion (MIR)injury utilizing signal transduction gene array, and the effects on the rats after injecting antidigoxin, endoxin specificness antagon.It was testified that endoxin 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 Birc1b 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 antidigoxin antiserum 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 antiserum 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.

Key words: endoxin, ischemia reperfusion injury, myocardium, gene, apoptosis, inflammatory factor

中图分类号:

R965.2

郑建发, 柯永胜, 高文俊, 汪和贵. 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[J]. 中国临床药理学与治疗学, 2008, 13(8): 880-885.

ZHENG Jian-fa, KE Yong-sheng, GAO Wen-jun, WANG He-gui. Endoxin mediating myocardial ischemia reperfusion injury by effecting expression of apoptosis and inflammation genes[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(8): 880-885.

参考文献 17

[1]	Hamlyn JM, Lu ZR, Manunta P, et al.Observations on the nature, biosynthesis, secrection and significance of endogenous ouabain[J].Clin Exp Hypertens, 1998, 20(56):523-533.
[2]	Ke YS.Endoxin:a major factor regulating cardiovascular system[J].Acta Pharmacol Sin, 2001, 22(3):201-209.
[3]	Zhao ZQ, Morris CD, Budde JM, et al.Inhibition of myocardial apoptosis reduces infarct size and improves regional contractile dy sfunction during reperfusion[J].Cardiovasc Res, 2003, 59(1):132-142.
[4]	Qin F, Liang MC, Liang CS.Progressive left ventricular remodeling, myocyte apoptosis, and protein signaling cascades after myocardial infarction in rabbits[J].Biochim Biophys Acta, 2005, 1740(3):499-513.
[5]	Hong CY, Huang SS, TsaISK.Magnolol reduces infarct size and suppresses ventricular arrhythmia in rats subjected to coronary ligation [J].Clin Exp Pharmcol Physiol, 1996, 23(8):660-664.
[6]	Schena M.蛋白质芯片[M].北京:科学出版社, 2005.
[7]	Ke YS, Wang DG, Wang HG, et al.Endoxin antagonist lessens myocardial ischemia reperfusion injury[J].Cardiovas Drug Ther, 2004, 18(4):289-294.
[8]	Ke YS, Wang HG, Wang DG, et al.Endoxin-mediated myocardial ischemia reperfusion injury in rats in vitro[J]. Can J Physiol Pharmacol, 2004, 82(6):402-408.
[9]	汪和贵, 柯永胜, 王德国, 等.内洋地黄素介导大鼠心肌缺氧复氧损伤的实验研究[J].中华急诊医学杂志, 2005, 14(4):289-293.
[10]	王德国, 汪和贵, 柯永胜, 等.内洋地黄素拮抗剂对大鼠心肌缺血再灌注损伤的保护作用[J].中国药理学通报, 2004, 20(8):927-931.
[11]	Honda HM, Korge P, Weiss JN.Mitochondria and ischemia reperfusion injury[J].Ann N Y Acad Sci, 2005, 1047:248-258.
[12]	Zhao ZQ, Vinten-Johansen J.Myocardial apoptosis and ischemic preconditioning [J].Cardiovas Res, 2002, 55(3):438-455.
[13]	Donath S, LIP, Willenbockel C, et al.Apoptosis repressor with caspase recruitment domain is required for cardioprotection in response to biomechanical and ischemic stress [J].Circulation, 2006, 113(9):1203-1212.
[14]	Ke Ys, Liu ZF, Wang DG, et al.Effects of antidigoxin antiserum on endoxin levels, apoptosis and the expression of Bax and Bcl-2 protein in ischaemia-reperfusion myocardium[J].Clin Exp Pharmacol Physiol, 2004, 31(10):691-695.
[15]	Khoynezhad A, JalalIZ, TortolanIAJ.Apoptosis :pathophy siology and therapeutic implications for the cardiac surgeon[J].Ann Thorac Surg, 2004, 78(3):1109-1118.
[16]	PchejetskID, Kunduzova O, Dayon A, et al.Oxidative stress-dependent sphingosine kinase-1inhibition mediates monoamine oxidase A-associated cardiac cell apoptosis [J].Circ Res, 2007, 100(1):7-9.
[17]	Lu X, Hamilton JA, Shen J, et al.Role of tumor necrosis factor-alpha in myocardial dysfunction and apoptosis during hindlimb ischemia and reperfusion[J].Crit Care Med, 2006, 34(2):484-491.