目的: 观察天麻素对大鼠离体心肌缺血/再灌注 (I/R)损伤的影响。
方法: 将60只SD雄性大鼠随机分为6组,体重(250 ±30)g,每组10只,正常对照组(control)、缺血再灌注(I/R )组 、天麻素预适应(10、50、100、200μmol/L)组。应用 Langendorff 离体心脏灌注系统建立心肌缺血/再灌注损伤模型。除正常对照组外, 各组分别平衡灌注、 全心停灌各 30min,再灌注60min,采用心脏电生理指标、心肌酶学指标、心肌形态学变化(TTC染色)等三个层面来观察天麻素预处理对心肌缺血-再灌注损伤(MIRI)模型的影响,以评价不同浓度的天麻素在MIRI中有无心肌保护作用。
结果:天麻素预适应明显抑制I/R 引起的左心室发展压(LVDP)、左室内压上升/下降最大速率( ±dp/dtmax)的变化百分率下降, 冠脉流出液中肌钙蛋白(Trop-1)、肌红蛋白(MYO)、肌酸激酶同工酶(CK MB)、乳酸脱氢酶(LDH)、肌酸激酶(CK)、天门冬氨酸氨基转移酶(AST)、α-羟丁酸脱氢酶(α-HBDH) 释放减少,心肌组织内CK 活力降低 ,组织病理学损伤改变明显减轻 ,显著改善缺血/再灌注后的心功能, 且有明显的量效关系。
结论 :天麻素对I/R引起的心肌损伤有显著的拮抗作用,天麻素预适应可增加离体灌流心脏的LVDP和±dp/dtmax, 减少冠脉流出液中Trop-1、CK MB、LDH及CK等心肌酶的释放 ,减少心肌组织病理学损伤, 从而表现出对离体心脏的保护作用 。
Abstract
Objective: To characterize the effect of Gastrodin on the ischemia/ reperfusion I/R injury in rat hearts.
Methods: Male Sprague-Dawley rat(210-260g)were randomly assigned to 6 groups:control group(Con),ischemia/reperfusion group (I/R),pre group,pre+gas(10、50、100、200μmol/L), The isolated hearts were reperfused in the Langendorff model and were subjected to either continuous perfusion for 90min or 30min for balance,global ischemia and reperfusion respectively. Use of cardiac electrophysiology index, myocardial enzymes and myocardial morphological changes (TTC staining) to observe the three levels gastrodin preconditioning on myocardial ischemia - reperfusion injury model, To evaluate different concentrations gastrodin myocardial ischemia - reperfusion injury in the presence or absence of myocardial protection.
Conclusion: Gastrodin could protect myocardium against I/R injury in rats , which might be related with its effects of restoring cardiac function.
关键词
天麻素 /
缺血再灌注损伤 /
预适应
Key words
Gastrodin /
Ischemia and Reperfusion /
Preconditioning
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参考文献
[1]张勤, 杨云梅, 余国友.天麻素注射液对老年难治性高血压患者血压和血管活性物质影响的随机对照研究[J].中西医结合学报, 2008, 6(7):695-699
[2]Zhu L, Guan H, Cui C, Tian S, Yang D, Wang X, Zhang S, Wang L, Jiang H.Gastrodin inhibits cell proliferation in vascular smooth muscle cells and attenuates neointima formation in vivo. [J].Int J Mol Med, 2012, 30(5):1034-1040
[3]周敏,陆永利,郑世玲,黎家华.天麻素抗离体心肌缺血/在灌注损伤的作用. [J].辽宁中医药大学学报, 2009, 11(12):180-182
[4]Moens AL, Claeys MJ, Timmermans JP, Vrints CJ.Myocardial ischemia/ reperfusion -injury,a clinical view on a complex pathophysiological process.[J].Int J Cardiol, 2005, 100(2):179-190
[5]Raedschelders K, Ansley DM, Chen DD.The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion.[J].Pharmacol Ther, 2012, 133(2):230-255
[6]Forde RC, Fitzgerald DJ.Reactive oxygen species and platelet activation in reperfusion injury. [J].Circulation, 1997, 95(4):787-789
[7]Timmers L, Pasterkamp G, de Hoog VC, Arslan F, Appelman Y, de Kleijn DP.The innate immune response in reperfused myocardium.[J].Cardiovasc Res, 2012, 94(2):276-283
[8]Eltzschig HK, Eckle T.Ischemia and reperfusion—from mechanism to translation. [J].Cardiovasc Res, 2011, 17(11):1391-1401
[9]Morel O, Perret T, Delarche N, Labèque JN, Jouve B, Elbaz M, Piot C, Ovize M.Pharmacological approaches to reperfusion therapy. [J].Cardiovasc Res, 2012, 94(2):246-252
[10]陈雯,郭丽丽,王阶.中药防治心肌缺血再灌注损伤研究进展. [J].辽宁中医杂志, 2012, 39(6):1192-1195
[11]Yang P, Han Y, Gui L, Sun J, Chen YL, Song R, Guo JZ, Xie YN, Lu D, Sun L.Gastrodin attenuation of the inflammatory response in H9c2 cardiomyocytes involves inhibition of NF-κB and MAPKs activation via the phosphatidylinositol 3-kinase signaling.[J].Biochem Pharmacol, 2013, 85(8):1124-1133
[12]Murry CE,Jennings RB,Reimer KA. .Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986,74(5): 1124-1136.[J].Circulation, 1986, 74(5):1124-1136
[13]Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, Vinten-Johansen J.Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2003,285(2): H579-588.[J].Am J Physiol Heart Circ Physiol, 2003, 285(2):H579-588
[14]Sanada S, Komuro I, Kitakaze M.Pathophysiology of myocardial reperfusion injury: preconditioning,postconditioning,and translational aspects of protective measures. Am J Physiol Heart Circ Physiol.2011,301(5): H1723-1741.[J].Am J Physiol Heart Circ Physiol, 2011, 301(5):H1723-1741