聚合血紅蛋白對活體大鼠心肌缺血再灌注的保護作用_《華西醫學》

作者：

萬秦 ¹ , 包敏 ² , 李怡 ³

1 甘孜州人民醫院急診內科（四川甘孜州，626000） 2 甘孜州衛校附院內科住院部; 3 甘孜州人民醫院門診藥房;

關鍵詞：

聚合血紅蛋白冠心病缺血再灌注大鼠

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【摘要】　目的　通過建立活體大鼠心肌缺血再灌注模型，模擬人類冠心病，研究聚合血紅蛋白（PolyHb）在心肌缺血再灌注中的保護作用，探究PolyHb在冠心病領域中的保護和治療作用。　方法　將45只Sprague-Dawley（SD）大鼠隨機分成3組:實驗組（15只）、對照組（15只）、假手術組（15只），建立大鼠心肌缺血模型。實驗組建立動物模型后，結扎冠狀動脈35 min，并于結扎后5 min，通過SD大鼠尾靜脈按1 mL/min的速度注射1 mL（100 g/L）的PolyHb溶液。缺血完成后開放灌注120 min。對照組建立動物模型，結扎冠狀動脈35 min，并于結扎后5 min，通過SD大鼠尾靜脈按1 mL/min的速度注射1 mL生理鹽水。缺血完成后開放灌注120 min。假手術組僅建立動物模型，但不結扎冠狀動脈，也不再灌注。比較3組SD大鼠的血流動力學參數左室內壓最大上升和下降速率、心肌酶（血清肌酸激酶、乳酸脫氫酶）及病理學檢查（梗死心肌占總心肌面積的百分比），來衡量PolyHb的作用。　結果　與對照組比較，用PolyHb處理的實驗組可增強再灌注時左室內壓最大上升和下降速率（P lt;0.05），減少血液中血清肌酸激酶和乳酸脫氫酶的含量（P lt;0.05），并明顯減少心肌梗死面積百分比（P lt;0.05）。　結論　在心肌缺血的SD大鼠中，PolyHb可以有效的降低缺血再灌注損傷，從而達到心肌保護作用。
【Abstract】　Objective　 To investigate the protective effect of polymerized hemoglobin (PolyHb) for myocardial ischemia-reperfusion and explore the field of polymerized hemoglobin in the protection and treatment of human coronary heart disease, by simulating human coronary heart disease and establishing myocardial ischemia-reperfusion model in living rats.　Methods　 Forty-five Sprague-Dawley (SD) rats were randomly divided into 3 groups: experimental group (n=15), control group (n=15), and sham operation (SHAM) group (n=15). Rat models of myocardial ischemia-reperfusion were established. For the rats in the experimental group, we ligated their left coronary artery for 35 minutes, and injected 1 mL (100 g/L) PolyHb solution into their body at a speed of 1 mL/min 5 minutes later. After ischemia was completed, reperfusion was performed for 120 minutes. The procedures carried out for the rats in the control group were exactly the same except that the PolyHB solution was replaced by 1 mL saline solution. Ligation of the artery and reperfusion were not performed on the rats in the SHAM group. Hemodynamic parameters (maximal rising and falling rates of left ventricular pressure), enzymes (serum creatine kinase, lactate dehydrogenase) and results of histopathologic examinations (percentage of myocardial infarction area over the total myocardial area) were measured and compared among the three groups to evaluate the function of PolyHb.　Results　 Compared with the control group, the experimental group treated with PolyHb had higher maximum rising and falling rates of left ventricular pressure (P lt;0.05), lower blood levels of creatine kinase and lactate dehydrogenase (P lt;0.05), and lower percentage of myocardial infarction area over the total myocardial area (P lt;0.05).　Conclusion　 Polymerized hemoglobin can effectively reduce the ischemia-reperfusion injury and achieve myocardial protection in SD rats with myocardial ischemia.

引用本文： 萬秦,包敏,李怡. 聚合血紅蛋白對活體大鼠心肌缺血再灌注的保護作用. 華西醫學, 2011, 26(8): 1146-1149. doi: 復制

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2.	Giugliano RP, Newby LK, Harington RA, et al. The early glycoprotein Ⅱb/Ⅲa inhibition in non-ST-segment elevation acute coronary syndrome(EARLY ACS) trial: a randomized placebo-controlled trial evaluating the clinical benefits of early front-loaded eptifibatide in the treatment of patients with non-ST-segment elevation acute coronary syndrome--study design and rationale[J].Am Heart J, 2005; 149(6): 994-1002.
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4.	Weintraub WS, Spetus JA, Kolm P, et al. Effect of PCI on quality of life in patients with stable coronary disease[J].N Engl J Med, 2008, 359(7): 677-687.
5.	Piper HM, Garcia-Dorado D, Ovize M. A fresh look at reperfusion injury[J].Cardiovasc Res, 1998, 38(2): 291-300.
6.	Bolli R, Becker L, Gross G, et al. Myocardialprotectionat a crossroads: the need for translationinto clinical therapy[J]. Circ Res, 2004, 95(2): 125-134.
7.	McNeil CJ, Smith LD, Jenkins LD, et al. Hypotensive resuscitation using a polymerized bovine hemoglobin-based oxygen-carrying solution(HBOC-201) leads to reversal of anaerobic metabolism[J]. J Trauma, 2001, 50(6): 1063-1075.
8.	Li T, Yu R, Zhang HH, et al. A method for purification and viral inactivation of human placenta hemoglobin[J]. Artif Cells Blood Substit Immobil Biotechnol, 2006, 34(2): 175-188.
9.	Lum H, Roebuck KA. Oxidant stress and endothelial cell dysfunction[J]. Am J Physiol Cell Physiol, 2001, 280(4): 719-741.
10.	Kim JK, Pedram A, Razandi M, et al. Estrogen prevents cardiomyocyte apoptosis through inhibition of reactive oxygen species and differential regulation of p38 kinase isoforms[J]. J Biol Chem, 2006, 281(10): 6760-6767.
11.	Zhao ZQ. Oxidative stress-elicited myocardial apoptosis during reperfusion[J]. Curr Opin Pharmacol, 2004, 4(2): 159-165.
12.	Scarabelli TM, Knight R, Stephanou A, et al. Clinical implications of apoptosis in ischemic myocardium[J]. Curr Probl Cardiol, 2006, 31(3): 181-264.

1. 　Yellon DM, Hausenloy DJ. Myocardial reperfusion injury[J]. N Engl J Med, 2007, 357(11): 1121-1135.
2. 　Giugliano RP, Newby LK, Harington RA, et al. The early glycoprotein Ⅱb/Ⅲa inhibition in non-ST-segment elevation acute coronary syndrome(EARLY ACS) trial: a randomized placebo-controlled trial evaluating the clinical benefits of early front-loaded eptifibatide in the treatment of patients with non-ST-segment elevation acute coronary syndrome--study design and rationale[J].Am Heart J, 2005; 149(6): 994-1002.
3. 　Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease[J]. N Engl J Med, 2009, 360(10): 961-972.
4. 　Weintraub WS, Spetus JA, Kolm P, et al. Effect of PCI on quality of life in patients with stable coronary disease[J].N Engl J Med, 2008, 359(7): 677-687.
5. 　Piper HM, Garcia-Dorado D, Ovize M. A fresh look at reperfusion injury[J].Cardiovasc Res, 1998, 38(2): 291-300.
6. 　Bolli R, Becker L, Gross G, et al. Myocardialprotectionat a crossroads: the need for translationinto clinical therapy[J]. Circ Res, 2004, 95(2): 125-134.
7. 　McNeil CJ, Smith LD, Jenkins LD, et al. Hypotensive resuscitation using a polymerized bovine hemoglobin-based oxygen-carrying solution(HBOC-201) leads to reversal of anaerobic metabolism[J]. J Trauma, 2001, 50(6): 1063-1075.
8. 　Li T, Yu R, Zhang HH, et al. A method for purification and viral inactivation of human placenta hemoglobin[J]. Artif Cells Blood Substit Immobil Biotechnol, 2006, 34(2): 175-188.
9. 　Lum H, Roebuck KA. Oxidant stress and endothelial cell dysfunction[J]. Am J Physiol Cell Physiol, 2001, 280(4): 719-741.
10. 　Kim JK, Pedram A, Razandi M, et al. Estrogen prevents cardiomyocyte apoptosis through inhibition of reactive oxygen species and differential regulation of p38 kinase isoforms[J]. J Biol Chem, 2006, 281(10): 6760-6767.
11. 　Zhao ZQ. Oxidative stress-elicited myocardial apoptosis during reperfusion[J]. Curr Opin Pharmacol, 2004, 4(2): 159-165.
12. 　Scarabelli TM, Knight R, Stephanou A, et al. Clinical implications of apoptosis in ischemic myocardium[J]. Curr Probl Cardiol, 2006, 31(3): 181-264.

《華西醫學》

聚合血紅蛋白對活體大鼠心肌缺血再灌注的保護作用

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《華西醫學》

聚合血紅蛋白對活體大鼠心肌缺血再灌注的保護作用

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