肢体缺血预适应对大鼠心脏的保护作用
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摘要
目的研究肢体缺血预适应(LIP)对大鼠缺血再灌后心脏损伤的影响。
方法采用反复捆绑后肢造成缺血预适应的方法,观察其对心肌缺血再灌后心脏血流动力学、ST-段的影响、对心肌缺血再灌后梗死面积和形态学改变的影响,对心肌酶CK-MB和cTn-Ⅰ的影响以及对抗氧化物酶的影响。
结果与缺血再灌组比较,预适应对心肌缺血再灌后HR和MAP的影响不具显著性差异,但是LIP能明显推迟心律失常出现的时间,缩短持续时间,降低心律失常的发生率,降低ST段的抬高幅度,并且能减少心肌梗死面积,降低心肌细胞的损害,减少心肌酶的漏出并能提高SOD的活性。
结论LIP对心肌损伤具有保护作用。
Objective:To observe the effect of limb ischemic preconditioning(LIP) on the myocardial ischemia-reperfusion(I/R) injury in rats.
Method:Using ischemic preconditioning in hind limb model was to investigate the effect on myocardial physiology,ST-segment,the effect on myocardial infarct size and morphologic change,the effect on the enzyme of CK-MB and cTn-I after myocardial I/R.
Results:Compared with I/R,the difference Was not significant on HR and MAP,but the apperanc time of VA was delayed and the duration time was shorten,the incidence rate of VA was decreased,the elevation of ST-segment was decreased,the myocardial infarct size was reduced,the myocardial injury was attenuated,the leakage of CK-MB and cTn-I were decreased and the activity of SOD was increased after pretreated with LIP. Conclusion:LIP could protect against myocardial injury.
方法采用反复捆绑后肢造成缺血预适应的方法,观察其对心肌缺血再灌后心脏血流动力学、ST-段的影响、对心肌缺血再灌后梗死面积和形态学改变的影响,对心肌酶CK-MB和cTn-Ⅰ的影响以及对抗氧化物酶的影响。
结果与缺血再灌组比较,预适应对心肌缺血再灌后HR和MAP的影响不具显著性差异,但是LIP能明显推迟心律失常出现的时间,缩短持续时间,降低心律失常的发生率,降低ST段的抬高幅度,并且能减少心肌梗死面积,降低心肌细胞的损害,减少心肌酶的漏出并能提高SOD的活性。
结论LIP对心肌损伤具有保护作用。
Objective:To observe the effect of limb ischemic preconditioning(LIP) on the myocardial ischemia-reperfusion(I/R) injury in rats.
Method:Using ischemic preconditioning in hind limb model was to investigate the effect on myocardial physiology,ST-segment,the effect on myocardial infarct size and morphologic change,the effect on the enzyme of CK-MB and cTn-I after myocardial I/R.
Results:Compared with I/R,the difference Was not significant on HR and MAP,but the apperanc time of VA was delayed and the duration time was shorten,the incidence rate of VA was decreased,the elevation of ST-segment was decreased,the myocardial infarct size was reduced,the myocardial injury was attenuated,the leakage of CK-MB and cTn-I were decreased and the activity of SOD was increased after pretreated with LIP. Conclusion:LIP could protect against myocardial injury.
引文
[1]Murry CE,Jennings RB,and Reimer KA.Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium[J].Circulation,1986,74(5):1124-36.
[2]Przyklenk K,Barbara B,Ovize M.Regional ischemic ‘preconditioning'protects remote virgin myocardium from subsequence sustained coronary occlusion[J].Circulation,1993,7:893-9.
[3]McClanahan TB,Nao BS,Wolke LJ.Brief renal occlusion and reperfusion induces myocardial size in rabbit[J].FASEB J,1993,7:Al18.
[4]Ferencz A,Racz B,Gasz Bet al.Intestinal ischemic preconditioning in rats and NF-kappaB activation[J].Microsurgery,2006,26(1):54-7.
[5]Moses MA,Addison PD,Neligan PC et al.Mitochondrial KATP channels in hindlimb remote ischemic preconditioning of skeletal muscle against infarction[J].Am J Physiol Heart Circ Physiol,2005,288:H559-67.
[6]Lang SC,Elsasser A,Scheler C et al.Myocardial preconditioning and remote renal preconditioning-identifying a protective factor using proteomic methods[J]? Basic Res Cardiol,2006,101(2):149-58.
[7]徐淑云,卞如濂,陈修主编.药理实验方法学[M].北京:人民出版社,2001:1042-3.
[8]London B.A precondition for arrhythmias[J].J Cardiovasc Electrophysiol.2007 Jan;18(1):100-1.
[9]徐淑云,卞如濂,陈修主编.药理实验方法学[M].北京:人民出版社,2001:1055-8.
[10]Vahlhaus C,Neumann J,Luss H,Wenzelburger F,Tjan TD,Hammel D,Scheld HH,Schmitz W,Breithardt G,Wichter T.Ischemic preconditioning by unstable angina reduces the release of CK-MB following CABG and stimulates left ventricular HSP-72 protein expression[J].J Card Surg.2005 Sep-Oct;20(5):412-9.
[11]Kharbanda RK,Li J,Konstantinov IE,Cheung MM,White PA,Frndova H,Stokoe J,Cox E Vogel M,Van Arsdell G,MacAllister R,Redington AN.Remote ischaemic preconditioning protects against cardiopulmonary bypass-induced tissue injury:a preclinical study[J].Heart.2006 Oct;92(10):1506-11.
[12]Beguin PC,Belaidi E,Godin-Ribuot D,Levy P,Ribuot C.Intermittent hypoxia-induced delayed cardioprotection is mediated by PKC and triggered by p38 MAP kinase and Erkl/2[J].J Mol Cell Cardiol.2007 Feb;42(2):343-51.
[13]Tang XL,Kodani E,Takano H,Hill M,Shinmura K,Vondriska TM,Ping E Bolli R:Protein tyrosine kinase signaling is necessary for NO donor-induced late preconditioning against myocardial stunning[J].Am J Physiol Heart Circ Physiol.2003 Apr;284(4):H1441-8.
[14]Zhang SZ,Xia Q,Cao CM,Gao Q,Bruce IC.The Mitochondrial Calcium Uniporter participates in Ischemia/Reperfusion Injury and in Cardioprotection by Ischemic Preconditioning[J].Conf Proc IEEE Eng Med Biol Soc.2004;5:3625-7.
[15]Aguilar A,Alvarez-Vijande R,Capdevila S et al.Antioxidant patterns (superoxide dismutase,glutathione reductase,and glutathione peroxidase) in kidneys from non-heart-beating-donors:experimental study [J].Transplant Proc,2007,39(1):249-52.
[16]Kazimoglu K,Bozkurt AK,Suzer O et al.The role of antioxidant supplementation in cardiac transplantation:an experimental study in rats [J].Transplant Proc,2004,36(10):2939-43
1.Tsang A,Hausenloy DJ,Mocanu MM,et al.Post conditioning a form of “modified reperfusion”protects the myocardium byactivating the phosphatidylinositol 3-kinase-Akt pathway[J].Cir Res,2004,95(3):230-232
2.Kaljusto ML,Mori T,Mohammad Husain Rizvi S,et al.Postcondi-tioning in rats and mice[J].Scand Cardiovasc J,2006,40(6):334-341.
3.Vinten-Johansen J,Yellon DM,Opre LH.Postconditioning:A simple,clinically applicable procedure to improve revascularization in acute myocardial infarction[J].Circulation,2005,112(14):2085-2088.
4.Staat P,Rioufol G,Piot C,et al.Postconditioning the humam heart[J].Circulation,2005,112(14):2143-2148.
5.Henriques JP,Gheeraert PJ,Ottervanger JP,et al.Ventricular fibrillation in acute myocardial infarction before and during primary PCI[J].Int J Cardiol,2005,105(3):262-266.
6.Murry CE,Jennings RB,Reimer KA.Preconditioning with Ischemia:a delay of lethal cell injury in ischemic myocardium[J].Circulation,1986,74(5):1124-1136.
7.Yellon DM,Alkhulaifi AM,Pugsley WB.Preconditioning the human myocardium[J].Lancet,1993,342(8866):276-277.
8.Katayama O,Ledinghain SJM,Amrari M,et al.Functional and metabolic effccts of adenosine in cardioplegia:Role of temperature and concentration[J].Ann Thorac S urg,1997,63(2):449-455.
9.Joyeux-Faure M,Ramond A,BeguinPC,et al.Early pharmacological preconditioning by erythropoietin mediated by inducible NOS and mitochondrial ATP-dependent potassiumchannels in the rat[J],heart.Fundam Clin Pharmacol,2006,20(1):51-56.
10.Zhao ZQ,Corvers JS,Halkos ME,et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion:comparison with ischemic preconditioning[J].Am J Physiol Heart Cric Physiol,2003,285(1):H579-H588.
11.Kin H,Zhao ZQ,Sun HY,et al.Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion[J].Cardiovasc Res,2004,62:74-85.
12.Philipp S,Yang XM,Cui L,et al.Postconditioning protects rabbit hearts through a protein kinsseC-adenosine A2b receptor cascade[J].Cardiovasc Res,2006,70(2):308-314.
13.Yang XM,Proctor JB,Cui L,et al.Multiple,brief coronary occlusions during early reperfuion protect rabbit hearts by targeting cell signaling pathways[J].J Am Coil Cardiol,2004,44:1103-1110.
14.彭龙云,马虹,何建桂,等.缺血后处理减轻大鼠肥厚心肌缺再灌注损伤的观察[J].中华心血管病杂志,2006,34(8):685-689.
15.GalagudzaM,KurapeevD,MinasianasS,et al.Ischemicpostcondition-ing:brief ischemia during reperfusion converts persistent ventricular fibrillation into regular rhythm[J].Eur J Cardiothorac Surg,2004,25:1006-1010.
16.Halkos ME,Karendi F,CorveraJS,et al.Myocardial protection with postcoditioning is not enhanced by ischemic preconditioning[J].Ann Thorac Surg,2004,78:961-969.
17.Roemer G,Dsllaporta B,Rescherigon M.The mitochondrial Death/life regulator in apoptosis and necrosis[J].Ann Rev Physiol,1998,60:619-642.
18.Argaud L,Gateau-Roesch O,Raisky O,et al.Postconditioning inhibits mitochondrial permeability transition[J].Circulation,2005,111:194-197.
19.Tessier-Vetzel D,Tissier R,Waintraub X,et al.Isoflurane inhaled at the onset of reperfusion potentiates the cardioprotective effect of ischemic postconditioning through a NO-dependent mechanism[J].J Cardvasc Pharmacol,2006,47(3):487-492.
20.Loukogeorgakis SP,Panagiotidou AT,Yellon DM,et al.Postconditioning protectsagainst endothelial ischemia-reperfusion injury in the human forearm[J].Circulation,2006,113:1015-1019.
21.Gross ER,Gross GJ.Ligand triggers of classical preconditioning and postconditioning[J].Cardiovasc Res,2006,70(2):212-221.
22.Ma X,Zhang X,Li C,et al.Effect of postconditioning on coronary blood flow velocity and endothelial function and LV recovery after myocardial infarction[J].Interv Cardiol,2006,19(5):367-375.
23.Weihrauch D,Krolikowski JG,Bienengraeber M,et al.Morphine enhances isoflurane-induced postconditioning against myocardial infarction:the role of phosphatidylinositol-3-kinase and opioid receptors in rabbits[J].Anesth Analg,2005,101(4):942-949.
24.Bose AK,Mocanu MM,Carr RD,et al.Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury[J].Diabetes,2005,54(1):146-151.
25.魏君.复方丹参滴丸对冠心病患者血流流变学的影响[J].中国微循环,2001,5(2):146-147.
26.韦星,杨永宗,郑军,等.蛋白激酶 C 在硝酸甘油诱导的心肌延迟保护中的作用观察[J].南华大学学报·医学版,2005,33(1):37-40.
27.周游,张季,赵瑛,等.复方丹参对缺血预适应大鼠心肌蛋白激酶 C 表达的影响[J].中草药,2003,34(10):34-46.
28.Chultz J,Rose E,Yao Zhenhai,et al.Evidence for involvement of opioid receptors in ischemic preconditioning in rat heart[J],mJ Physiol,1995,268(37):2157-2161.
29.SchultzJ,HsuA,GrossG.Morphine mimics the cardioprotective effect of ischemic preconditioning via a glibenclamide-sensitive mechanism in the rat heart[J].Circ Res,1996,78:1100-11043.
30.Miki T,Cohen M,Downey J.Opioid receptor contributes to ischemic preconditioning through protein kinase C activation in rabbits[J].Mol Cell Biochem,1998,186:3-12.
[2]Przyklenk K,Barbara B,Ovize M.Regional ischemic ‘preconditioning'protects remote virgin myocardium from subsequence sustained coronary occlusion[J].Circulation,1993,7:893-9.
[3]McClanahan TB,Nao BS,Wolke LJ.Brief renal occlusion and reperfusion induces myocardial size in rabbit[J].FASEB J,1993,7:Al18.
[4]Ferencz A,Racz B,Gasz Bet al.Intestinal ischemic preconditioning in rats and NF-kappaB activation[J].Microsurgery,2006,26(1):54-7.
[5]Moses MA,Addison PD,Neligan PC et al.Mitochondrial KATP channels in hindlimb remote ischemic preconditioning of skeletal muscle against infarction[J].Am J Physiol Heart Circ Physiol,2005,288:H559-67.
[6]Lang SC,Elsasser A,Scheler C et al.Myocardial preconditioning and remote renal preconditioning-identifying a protective factor using proteomic methods[J]? Basic Res Cardiol,2006,101(2):149-58.
[7]徐淑云,卞如濂,陈修主编.药理实验方法学[M].北京:人民出版社,2001:1042-3.
[8]London B.A precondition for arrhythmias[J].J Cardiovasc Electrophysiol.2007 Jan;18(1):100-1.
[9]徐淑云,卞如濂,陈修主编.药理实验方法学[M].北京:人民出版社,2001:1055-8.
[10]Vahlhaus C,Neumann J,Luss H,Wenzelburger F,Tjan TD,Hammel D,Scheld HH,Schmitz W,Breithardt G,Wichter T.Ischemic preconditioning by unstable angina reduces the release of CK-MB following CABG and stimulates left ventricular HSP-72 protein expression[J].J Card Surg.2005 Sep-Oct;20(5):412-9.
[11]Kharbanda RK,Li J,Konstantinov IE,Cheung MM,White PA,Frndova H,Stokoe J,Cox E Vogel M,Van Arsdell G,MacAllister R,Redington AN.Remote ischaemic preconditioning protects against cardiopulmonary bypass-induced tissue injury:a preclinical study[J].Heart.2006 Oct;92(10):1506-11.
[12]Beguin PC,Belaidi E,Godin-Ribuot D,Levy P,Ribuot C.Intermittent hypoxia-induced delayed cardioprotection is mediated by PKC and triggered by p38 MAP kinase and Erkl/2[J].J Mol Cell Cardiol.2007 Feb;42(2):343-51.
[13]Tang XL,Kodani E,Takano H,Hill M,Shinmura K,Vondriska TM,Ping E Bolli R:Protein tyrosine kinase signaling is necessary for NO donor-induced late preconditioning against myocardial stunning[J].Am J Physiol Heart Circ Physiol.2003 Apr;284(4):H1441-8.
[14]Zhang SZ,Xia Q,Cao CM,Gao Q,Bruce IC.The Mitochondrial Calcium Uniporter participates in Ischemia/Reperfusion Injury and in Cardioprotection by Ischemic Preconditioning[J].Conf Proc IEEE Eng Med Biol Soc.2004;5:3625-7.
[15]Aguilar A,Alvarez-Vijande R,Capdevila S et al.Antioxidant patterns (superoxide dismutase,glutathione reductase,and glutathione peroxidase) in kidneys from non-heart-beating-donors:experimental study [J].Transplant Proc,2007,39(1):249-52.
[16]Kazimoglu K,Bozkurt AK,Suzer O et al.The role of antioxidant supplementation in cardiac transplantation:an experimental study in rats [J].Transplant Proc,2004,36(10):2939-43
1.Tsang A,Hausenloy DJ,Mocanu MM,et al.Post conditioning a form of “modified reperfusion”protects the myocardium byactivating the phosphatidylinositol 3-kinase-Akt pathway[J].Cir Res,2004,95(3):230-232
2.Kaljusto ML,Mori T,Mohammad Husain Rizvi S,et al.Postcondi-tioning in rats and mice[J].Scand Cardiovasc J,2006,40(6):334-341.
3.Vinten-Johansen J,Yellon DM,Opre LH.Postconditioning:A simple,clinically applicable procedure to improve revascularization in acute myocardial infarction[J].Circulation,2005,112(14):2085-2088.
4.Staat P,Rioufol G,Piot C,et al.Postconditioning the humam heart[J].Circulation,2005,112(14):2143-2148.
5.Henriques JP,Gheeraert PJ,Ottervanger JP,et al.Ventricular fibrillation in acute myocardial infarction before and during primary PCI[J].Int J Cardiol,2005,105(3):262-266.
6.Murry CE,Jennings RB,Reimer KA.Preconditioning with Ischemia:a delay of lethal cell injury in ischemic myocardium[J].Circulation,1986,74(5):1124-1136.
7.Yellon DM,Alkhulaifi AM,Pugsley WB.Preconditioning the human myocardium[J].Lancet,1993,342(8866):276-277.
8.Katayama O,Ledinghain SJM,Amrari M,et al.Functional and metabolic effccts of adenosine in cardioplegia:Role of temperature and concentration[J].Ann Thorac S urg,1997,63(2):449-455.
9.Joyeux-Faure M,Ramond A,BeguinPC,et al.Early pharmacological preconditioning by erythropoietin mediated by inducible NOS and mitochondrial ATP-dependent potassiumchannels in the rat[J],heart.Fundam Clin Pharmacol,2006,20(1):51-56.
10.Zhao ZQ,Corvers JS,Halkos ME,et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion:comparison with ischemic preconditioning[J].Am J Physiol Heart Cric Physiol,2003,285(1):H579-H588.
11.Kin H,Zhao ZQ,Sun HY,et al.Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion[J].Cardiovasc Res,2004,62:74-85.
12.Philipp S,Yang XM,Cui L,et al.Postconditioning protects rabbit hearts through a protein kinsseC-adenosine A2b receptor cascade[J].Cardiovasc Res,2006,70(2):308-314.
13.Yang XM,Proctor JB,Cui L,et al.Multiple,brief coronary occlusions during early reperfuion protect rabbit hearts by targeting cell signaling pathways[J].J Am Coil Cardiol,2004,44:1103-1110.
14.彭龙云,马虹,何建桂,等.缺血后处理减轻大鼠肥厚心肌缺再灌注损伤的观察[J].中华心血管病杂志,2006,34(8):685-689.
15.GalagudzaM,KurapeevD,MinasianasS,et al.Ischemicpostcondition-ing:brief ischemia during reperfusion converts persistent ventricular fibrillation into regular rhythm[J].Eur J Cardiothorac Surg,2004,25:1006-1010.
16.Halkos ME,Karendi F,CorveraJS,et al.Myocardial protection with postcoditioning is not enhanced by ischemic preconditioning[J].Ann Thorac Surg,2004,78:961-969.
17.Roemer G,Dsllaporta B,Rescherigon M.The mitochondrial Death/life regulator in apoptosis and necrosis[J].Ann Rev Physiol,1998,60:619-642.
18.Argaud L,Gateau-Roesch O,Raisky O,et al.Postconditioning inhibits mitochondrial permeability transition[J].Circulation,2005,111:194-197.
19.Tessier-Vetzel D,Tissier R,Waintraub X,et al.Isoflurane inhaled at the onset of reperfusion potentiates the cardioprotective effect of ischemic postconditioning through a NO-dependent mechanism[J].J Cardvasc Pharmacol,2006,47(3):487-492.
20.Loukogeorgakis SP,Panagiotidou AT,Yellon DM,et al.Postconditioning protectsagainst endothelial ischemia-reperfusion injury in the human forearm[J].Circulation,2006,113:1015-1019.
21.Gross ER,Gross GJ.Ligand triggers of classical preconditioning and postconditioning[J].Cardiovasc Res,2006,70(2):212-221.
22.Ma X,Zhang X,Li C,et al.Effect of postconditioning on coronary blood flow velocity and endothelial function and LV recovery after myocardial infarction[J].Interv Cardiol,2006,19(5):367-375.
23.Weihrauch D,Krolikowski JG,Bienengraeber M,et al.Morphine enhances isoflurane-induced postconditioning against myocardial infarction:the role of phosphatidylinositol-3-kinase and opioid receptors in rabbits[J].Anesth Analg,2005,101(4):942-949.
24.Bose AK,Mocanu MM,Carr RD,et al.Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury[J].Diabetes,2005,54(1):146-151.
25.魏君.复方丹参滴丸对冠心病患者血流流变学的影响[J].中国微循环,2001,5(2):146-147.
26.韦星,杨永宗,郑军,等.蛋白激酶 C 在硝酸甘油诱导的心肌延迟保护中的作用观察[J].南华大学学报·医学版,2005,33(1):37-40.
27.周游,张季,赵瑛,等.复方丹参对缺血预适应大鼠心肌蛋白激酶 C 表达的影响[J].中草药,2003,34(10):34-46.
28.Chultz J,Rose E,Yao Zhenhai,et al.Evidence for involvement of opioid receptors in ischemic preconditioning in rat heart[J],mJ Physiol,1995,268(37):2157-2161.
29.SchultzJ,HsuA,GrossG.Morphine mimics the cardioprotective effect of ischemic preconditioning via a glibenclamide-sensitive mechanism in the rat heart[J].Circ Res,1996,78:1100-11043.
30.Miki T,Cohen M,Downey J.Opioid receptor contributes to ischemic preconditioning through protein kinase C activation in rabbits[J].Mol Cell Biochem,1998,186:3-12.