期刊文献+

三甲氧苄嗪对低流量灌流大鼠心肌细胞葡萄糖转运蛋白-1、4mRNA表达的影响 被引量:1

Effect of Trimetazidine and Low Flow Ischemia on the Expression of GLUT - 1 and GLUT - 4 mRNA in the Isolated Perfused Rat Heart
暂未订购
导出
摘要 目的:通过离体心脏灌注模型,观察低流量缺血及TMZ对大鼠心肌细胞葡萄糖转运蛋白-1、4(glucose transportertypel、4,GLUT1/4)mRNA表达的影响。方法:成年、雄性Wistar大鼠,分为:(1)对照组(N);(2)缺血再灌注组(R);(3)缺血组(I);(4)预处理/缺血(PI);(5)预处理/缺血/再灌注组(PR)。另取12只雄性Wistar大鼠,喂以TMZ14日,随机分为TMZ对照组(TC)和TMZ缺血/再灌注组(TR)。各组均测定灌流液LDH、CK含量,并用RT-PCR方法观察心肌GLUT-1/GLUT-4mRNA表达的变化。结果:预处理和TMZ饲喂明显降低心肌缺血及再灌注期间LDH和CK的释放;GLUT-1mRNA含量:I组、B组、PI组、PR组、TC组和TR组明显高于正常对照组(P值均小于0.05);R组、PI组和PR组含量明显低于I组(P值均小于0.05);PR组和R组或PI组间比较,差值没有显著意义;TR组GLUT-1mRNA含量明显高于R组及PR组(P值均小于0.05);而TR组和I组比较则无显著差异。各组间GLUT-4mRNA含量变异大,没有显著差异。结论:低流量缺血显著增加了心肌GLUT-1mRNA的表达,而对GLUT-4mRNA的含量没有显著的影响;而再灌注后,GLUT-1mRNA含量较再灌注开始前有所下降,但仍高于基础状态。口服TMZ增加非缺血心肌在正常氧供状态下GLUT-1mRNA表达,有助于提高心脏对低流量缺血的耐受性。 Objective: Myocardial ischemia increases heart glucose utilization in vivo. But whether oral TMZ could alter the level of mRNA expression of GLUT - 1 and GLUT - 4 is not fully investigated. Method: 30 adult, male Wistar rats were assigned random-lyinto:(1)normal(N) ; (2)ischemia/reperfusion(R) ; (3)ischemia(I) ; (4)preconditioning/ischemia(PI) ;(5)preconditioning/ischemi-a/reperfusion(PR) . An additional 12 rats were fed with trimetazidine (TMZ) for 2 weeks, and assigned into group TMZ control (TC) and TMZ ischemia/reperfusion (TR) . LDH and Ck leakage during ischemia and reperfusion were assessed. And the mRNA expressions of GLUT - 1 and GLUT - 4 in rat myocytes were measured using RT - PCR method with internal standard. Result: preconditioning and oral TMZ significantly reduce the LDH and CK release during reperfusion. For GLUT - 1 mRNA contents, those of group I, R, PI, PR, TC and TR were significantly higher than that of group N . And in group R, PI and PR, they are lower than group I. No difference was found between group Pr, Pi and R . The mRNA expression of GLUT - 1 significantly in group TR compared with group R and PR. No difference was found among the GLUT - 4 mRNA expressions of those groups. Conclusion: low flow ischemia significantly increased the GLUT - 1 mRNA expression, but had little effect on the mRNA content of GLUT - 4. After reperfusion, the GLUT - 1 mRNA content decreased slightly, but still above basal level. Oral TMZ can increase the GLUT - 1 mRNA content of myocytes under normoxia conditions, and thus would help the heart less susceptible to ischemia/reperfusion injuries.
出处 《中国医药导刊》 2001年第5期380-382,384,共4页 Chinese Journal of Medicinal Guide
关键词 心肌缺血 葡萄糖转运蛋白 三甲氧苄嗪 心肌保护 动物实验 myocardial ischemia, glucose transporter, trimetazidine
  • 相关文献

参考文献14

  • 1Lazar HL. Enhanced preservation of acutely ischemic myocardium using glucoseinulin - potassium solutions. J Card Surg, 1994; 9(3): Suppl, 474~ 478
  • 2Taegtmeyer H, et al.Substrate metabolism as a determinant for postischemic functional recovery of the heart. Am J Cardiol. 1997;80(3A) :3A ~ 10A
  • 3DeussenA, et al; [Metabolic aapects of myocardial ischemia] Z Kardiol, 1998;87: Suppl,37 ~ 40
  • 4Mody FV, Singh BN, Mohiuddin IH, et al. Trimetazidine - induced enhancement of myocardial glucose utilization in normal and ischemic myocardial tissue: an evaluation by positron emission tomography. Am J Cardiol, 1998 Sep 3, 82:5A, 42K ~ 49K
  • 5Doris - Medina CL, Lund DD, Pasley A, et al. Immunolo - calization of GLUT - 1 glucose transporter in rat skeletal muscle and in normal and hypoxic cardiac tissue. Am J Physiol1993;265:E454 ~ E464
  • 6Slot JW, Geuze HJ, Gigengack S, et al. Translocation of the glucose transporter GLUT4 in cardiac myocytes of the rat. Proc Nad Acad Sci USA 1991;88:7815 ~ 7819
  • 7Brosius F. C., Liu Y., Nguyen N., et al. Persistent myocardial ischemia increases GLUT1 glucose transporter expression in both ischemic and non - ischemic heart regions. J Mol Cell Cardiol . 1997;29:1675 ~ 1685
  • 8Sivitz W. I., Lund D. D., Yorek B., et al. Pretranslational regulation of two cardiac glucose transporters in rats exposed to hypobaric hypoxia. Am J Physiol. 1992; 263: E562 ~ E569
  • 9Young L. H., Renfu Y. Low - flow ischemia leads to translocation of canine heart GLUT - 4 and GLUT - 1 glucose transporters to the sar - colemma in vivo. Circulation .1997; 95: 415~ 422
  • 10L. H. Opie. Metabolic perturbations in ischemic heart disease. Dialogues in Cardiovascular medicine, 1996; 1(2)

二级参考文献6

  • 1Lu C,Am J Cardiol,1998年,82卷,7期,898页
  • 2Guarnieri C,Basic Res Cardiol,1997年,92卷,2期,90页
  • 3Veitch K,Am J Cardiol,1995年,76卷,6期,25B页
  • 4Astarie Dequeker C,J Cardiovasc Pharmacol,1994年,23卷,3期,401页
  • 5Koning M M,Cardiovasc Drugs Ther,1993年,7卷,5期,807页
  • 6Devynck M A,Eur J Pharmacol,1993年,245卷,2期,105页

共引文献1

同被引文献21

  • 1Taegtmeyer H, King LM, Jones BE. Energy substrate metabolism,myocardial ischemia, and targets for pharmacotherapy. Am J Cardiol,1998; 82(5A) : 54K - 60K.
  • 2Kantor PF,Lucien A, Kozak R, et al. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long - chain 3 - ketoacyl coenzyme A thiolase. Circ Res, 2000; 86(5): 580-588.
  • 3Minners J, van - den - Bos EJ, Yellon DM, et al. Dinitmphenol, cyclosporin A, and trimetazidine modulate preconditioning in the isolated rat heart: support for a mitochondrial role in cardioprotection. Cardiovasc Res, 2000; 47(1): 68-73.
  • 4El Banani H, Bernard M, Baetz D, et al. Changes in intracellular sodium and pH during ischaemia - reperfusion are attenuated by trimetazidine.Comparison between low-and zero- flow ischaemia. Cardiovasc Res,2000; 47(4) : 688-696.
  • 5Szwed H, Sadowski Z, Elikowski W, et al. Combination treatment in stable effort angina using trimetazidine and metoprolol: results of a randomized, double-blind, multicentre study (TRIMPOL Ⅱ). TRIMetazidine in POLand. Eur Heart J, 2001 ; 22(24) : 2267 - 74.
  • 6Manchanda SC. Treatment of stable angina with low dose diltiazem in combination with the metabolic agent trimetazidine. Int J Cardiol, 2003;88(1) : 83-89.
  • 7Hanania G, Haiat R, et al; groupe des investigatems ETICC. Coronary artery disease observed in general hospitals: ETTIC study. Comparison between trimetazidine and mononitrate isosorbide for patients receiving betablockers . Ann Cardiol Angeiol (Paris), 2002;51(5):268-274.
  • 8Marzilli M, Klein WW. Efficacy and tolerability of trimetazidine in stable angina : a meta - analysis of randomized, double - blind, controlled trials. Coron Artery Dis, 2003; 14(2) : 171 - 179.
  • 9Fragasso G, Piatti PM, Monti L, et al. Acute effects of heparin administration on the ischemic threshold of patients with coronary artery disease: evaluation of the protective role of the metabolic modulator trimetazidine. J Am Coil Cardiol, 2002; 39(3) : 413 - 419.
  • 10Blardi P, de Lalla A, Volpi L, et al. Increase of adenosine plasma levels after oral trimetazidine: a pharmacological ptrvonditioning?Pharmacol Res, 2002; 45(1): 69-72.

引证文献1

二级引证文献1

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部