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脂联素对大鼠心肌缺血再灌注损伤的保护作用 被引量:6

Protective effects of adiponectin on myocardial ischemia-reperfusion injury in rats
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摘要 目的观察脂联素对大鼠心肌缺血再灌注损伤的保护作用并探讨其机制。方法32只8周龄雄性大鼠随机分为假手术组、缺血再灌注组、地尔硫革组和脂联素组,每组8只。(1)假手术组:只穿线,旷置90min。(2)缺血再灌注组:先阻断血流30rain,再灌注60min。(3)地尔硫革组和脂联素组:先阻断血流30min,于再灌注开始时,从鼠尾静脉分别注射地尔硫革(3.5μg·g-1·min-1)或脂联素(60ng·g-1·min-1),注射2min,再灌注60min。各模型组于再灌注60min后处死大鼠。测定心肌组织一氧化氮(NO),心肌组织半胱氨酸蛋白酶3(Caspase3)活性,心肌组织腺苷酸活化蛋白激酶(AMPK)活性,过氧化物酶体增殖物激活受体γ(PPARγ)的含量,同时用透射电镜观察大鼠心肌线粒体结构。结果(1)缺血再灌注组心肌组织中Caspase3活性显著高于假手术组[(168.50±30.08)txmol/L比(53.25±11.41)μmol/L,P〈0.01],AMPK活性、PPARγ含量均显著低于假手术组[(0.74±0.59)IU/ml比(25.63±4.61)IU/ml,P〈0.01;0.1894比0.7949,P〈0.01],心肌组织中NO含量显著低于假手术组[(6.359±1.355)μmol/L比(10.396±1.901)μmol/L,P〈0.01]。(2)脂联素组心肌组织中Caspase3活性显著低于缺血再灌注组[(88.75±6.92)μmol/L比(168.50±30.08)μmol/L,P〈0.01],AMPK活性、PPA聊含量均显著高于缺血再灌注组[(27.22±4.76)IU/ml比(0.74±0.59)IU/ml,P〈0.01;0.8613比0.1894,P〈0.01],心肌组织中NO含量显著高于缺血再灌注组[(15.755±1.045)txmol/L比(6.359±1.355)μmol/L,P〈0.01]。脂联素可保护急性心肌缺血再灌注过程中大鼠心肌细胞线粒体结构的完整性,上述作用优于地尔硫革。结论脂联素对缺血再灌注造成的心肌损伤有一定的保护作用,机制可能与其增加心肌细胞AMPK、PPA脚表达,以及抗心肌细胞凋亡作用有关。 Objective To investigate the protective effects of adiponectin on myocardial ischemia- reperfusion injury and the potential mechanisms in rats. Methods Thirty-two male rats aged 8 weeks were randomly assigned to sham operation (sham) , myocardial ischemia-reperfusion (MIR), dihiazem treatment (diltiazem) or adiponectin administration (APN) groups ( n = 8 each). MIR rats underwent left anterior descending artery(LAD) occlusion for 30 min followed by 60 min reperfusion. Diltiazem (7 μg/g) and APN (120 ng/g) were given by caudal intravenous injection at the end of 30 min ischemia and the beginning of repeffusion for rats in diltiazem or APN groups. Animals were sacrificed after 60 mira reperfusion for determining the myocardial nitric oxide ( NO), Caspase 3, activity of AMP-activated protein kinase(AMPK) and concentration of peroxisome proliferators-activaated receptor γ (PPARγ). Apoptotic cells were stained by Caspase 3 Activity Assay Kit and mitochondria in myocardial cells were observed by transmission electron microscope (TEM). Resldts The myocardial Caspase 3 level was significantly increased [ (168.50 ± 30. 08) μmol/L vs. (53.25 ± 11.41 ) μmol/L,P 〈0. 01 ], AMPK activity, PPARγ and NO concentrations were significantly reduced in MIR group compared with those in sham group ( all P 〈 0. 05 ) [ ( 0. 74 ± 0.59 ) IU/ml vs. (25.63 ±4.61)IU/rrd,P 〈0. 01; 0. 1894 vs. 0.7949,P〈0.01;(6.359±1.355) μmol/L vs. ( 10. 396 ± 1. 901 ) μmol/L,P 〈0. 01 ], these effects could be significantly reversed by APN. In comparison with MIR group, the levels of Caspase 3 in cardiac muscles were significantly lowered in Adiponectin group [ (88. 75 ± 6. 92 )μmol/L vs. ( 168. 50 ± 30. 08 ) μmo]/L, P 〈 0. 01 ], whereas the level of AMPK and PPARγ, NO concentration in the cardiac muscle was remarkably increased [ (27. 22 ± 4.76 )IU/ml vs. (0. 74 ± 0. 59) IU/ml, P 〈 0. 01 ; 0. 8613 vs. 0. 1894, P 〈 0. 01 ; ( 15. 755 ± 1. 045 ) μmol/L vs. ( 6. 359 ± 1. 355)μmol/L,P 〈 0. 01 ]. APN also preserved the function and structure of mitoehondria in rats post isehemia/reperfusion injury. The protective pharmacologic actions of APN were superior to that of diltiazem. Conclusion Adiponeetin could protect myocardial tissues from myocardial isehemia-reperfusion injury in rats, possibly by upregulating myocardial AMPK and PPARγ expressions and preventing myocardial cells from apoptosis.
出处 《中华心血管病杂志》 CAS CSCD 北大核心 2010年第3期252-258,共7页 Chinese Journal of Cardiology
关键词 心肌再灌注损伤 脂联素 细胞凋亡 Myocardial reperfusion injury Adiponeetin Apoptosis
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参考文献22

  • 1徐叔云,苄如濂,陈修.药理实验方法学.3版.北京:人民卫生出版社,2006:938.
  • 2Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose-specific protein, adiponeetin, in besity. Bioehem Biophys Res Commun, 1999, 257:79-83.
  • 3Shimada K, Miyazaki T, Daida H. Adiponectin and atherosclerotic disease. Clin Chim Acta,2004, 344 : 1-12.
  • 4Cavusoglu E, Chopra V, Battala V, et al. Baseline plasma adiponcctin levels as a predictor of left ventricular systolic dysfunction in patients referred for coronary angiography. Am J Cardiol,2008, 101 : 1073-1078.
  • 5Siller-Matula JM, Lang I, Christ G, et al. Calcium-channel blockers reduce the antiplatelet effect of clopidogrel. J Am Coll Cardiol, 2008,52:1564-1566.
  • 6Scarbelli T, Stephanou A, Rayment N, et at. Apoptosis of endothelial cells precedes myocyte cell apoptosis in ischemia/ reperfusion injury. Circulation ,2001,104:253-256.
  • 7Honda T, Kaikita K, Tsujita K, et al. Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates myocardial ischemia-reperfusion injury in mice with metabolic disorders. J Mol Cell Cardiol, 2008,44:915-926.
  • 8Elrod JW, Harrell M, Flagg TP, et al. Role of sulfonylurea receptor type 1 subunits of ATP-sensitive potassium channels in myocardial ischemia/reperfusion injury. Circulation, 2008,117 : 1405-1413.
  • 9Blokhin IO, Vlasov TD, Galagudza MM, et al. Role of sodium- calcium exchanger in myocardial protection against ischemia- reperfusion injury. Ross Fiziol Zh Im I M Sechenova, 2008, 94: 284 -292.
  • 10Black SC, Huang JQ, Rezaiefar P, et al. Co-localization of the cysteine protease caspase-3 with apoptotic myocytes after in vivo myocardial ischemia and reperfusion in the rat. J Mol Cell Cardiol, 1998,30:733-742.

二级参考文献98

  • 1Murry C,Jennings R,Reimer K.Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium.Circulation 1986; 74:1124-1136.
  • 2Yellon DM,Downey JM.Preconditioning the myocardium:from cellular physiology to clinical cardiology.Physiol Rev 2003; 83:1113-1151.
  • 3Bolli R.Preconditioning:a paradigm shift in the biology of myocardial ischemia.Am J Physiol 2007; 292:H19-H27.
  • 4Hausenloy DJ,Yellon DM.Survival kinases in ischemic preconditioning and postconditioning.Cardiovasc Res 2006; 70:240-253.
  • 5Das DK,Maulik N.Preconditioning potentiates redox signaling and converts death signal into survival signal.Arch Biochem Biophys 2003; 420:305-311.
  • 6Saini HK,Machackova J,Dhalla NS.Role of reactive oxygen species in ischemic preconditioning of subcellular organelles in the heart.Antioxid Redox Signal 2004; 6:393-404.
  • 7Cohen MV,Yang XM,Downey JM.Nitric oxide is a preconditioning mimetic and cardioprotectant and is the basis of many available infarct-sparing strategies.Cardiovasc Res 2006; 70:231-239.
  • 8Jones SP,Bolli R.The ubiquitous role of nitric oxide in cardioprotection.J Mol Cell Cardiol 2006; 40:16-23.
  • 9Seddon M,Shah AM,Casadei B.Cardiomyocytes as effectors of nitric oxide signalling.Cardiovasc Res 2007; 75:315-326.
  • 10Belge C,Massion PB,Pelat M,Balligand JL.Nitric oxide and the heart:update on new paradigms.Ann NY Acad Sci 2005; 1047:173-182.

共引文献8

同被引文献75

  • 1白书玲,李建军.C反应蛋白与动脉粥样硬化[J].中华心血管病杂志,2004,32(8):765-768. 被引量:133
  • 2蔡庆勇,梁贵友,牛义民,高振宇,宋宣统.体外循环心肌胰岛素抵抗的实验研究[J].遵义医学院学报,2006,29(4):347-350. 被引量:15
  • 3吴强,杨永曜,李隆贵,杨天和,蔡运昌,蒋清安.非诺贝特和吡格列酮对血管紧张素Ⅱ介导的心肌细胞肥大和凋亡的干预作用[J].中华高血压杂志,2007,15(3):233-237. 被引量:7
  • 4Maseri A.Inflammation,atherosclerosis,and ischemic events-exploring the hidden dide of the moon[J].N Engl J Med,1997,3369(2):1014-1016.
  • 5Berg AH,Scherer PE.Adipose tissue,inflammation and cardiovascular disease[J].Circ Res,2005,96 (9):939-949.
  • 6Lehrke M,Reilly MP,Millington SC,et al.An inflammatory cascade leading to hyperresistinemia in humans[J].PLoS Med,2004,1(2):e45.
  • 7Axelsson J,Bergsten A,QureshiAR,et al.Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation,but not with insulin resistance[J].Kidney Int,2006,69 (3):5962-6041.
  • 8Reilly MP,Lehrke M,Wolfe ML,et al.Resistin is an inflammat orymarker of atherosclerosis in humans[J].Circulation,2005,111(7):9322-9391.
  • 9Piestrzeniewicza K,Luczaka K,Komorowski,et al.Resistin increases with obesity and atherosclerotic risk factors in patients with myocardial infarction[J].Metab Clin Exp,2008,57(4):4882-4931.
  • 10Lubos E,Messow CM,Schnabel R,et al.Resistin,acute coronary syndrome and prognosis results from the Athero Gene study[J].Atherosclerosis,2007,193 (1):1212-1281.

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