Research on the Protective Effect of Polymerized Hemoglobin for Heart Muscles of Living Rats Undergoing Myocardial Ischemia-reperfusion_West China Medical Journal

Authors：

WAN Qin ¹ , BAO Min ² , LI Yi ³

1. Internal Medicine Branch of the Emergency Department, People′s Hospital of Ganzizhou, Ganzizhou, Sichuan 626000, P. R. China; 2. Inpatient Department of Internal Medicine, Affiliated Hospital of Ganzizhou School of Health, Ganzizhou, Sichuan 626000, P. R. China; 3. Outpatient Pharmacy, People′s Hospital of Ganzizhou, Ganzizhou, Sichuan 626000, P. R. China;

Corresponding author：

Keywords：

聚合血红蛋白; 冠心病; 缺血再灌注; 大鼠

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【摘要】　目的　通过建立活体大鼠心肌缺血再灌注模型，模拟人类冠心病，研究聚合血红蛋白（PolyHb）在心肌缺血再灌注中的保护作用，探究PolyHb在冠心病领域中的保护和治疗作用。　方法　将45只Sprague-Dawley（SD）大鼠随机分成3组:实验组（15只）、对照组（15只）、假手术组（15只），建立大鼠心肌缺血模型。实验组建立动物模型后，结扎冠状动脉35 min，并于结扎后5 min，通过SD大鼠尾静脉按1 mL/min的速度注射1 mL（100 g/L）的PolyHb溶液。缺血完成后开放灌注120 min。对照组建立动物模型，结扎冠状动脉35 min，并于结扎后5 min，通过SD大鼠尾静脉按1 mL/min的速度注射1 mL生理盐水。缺血完成后开放灌注120 min。假手术组仅建立动物模型，但不结扎冠状动脉，也不再灌注。比较3组SD大鼠的血流动力学参数左室内压最大上升和下降速率、心肌酶（血清肌酸激酶、乳酸脱氢酶）及病理学检查（梗死心肌占总心肌面积的百分比），来衡量PolyHb的作用。　结果　与对照组比较，用PolyHb处理的实验组可增强再灌注时左室内压最大上升和下降速率（P lt;0.05），减少血液中血清肌酸激酶和乳酸脱氢酶的含量（P lt;0.05），并明显减少心肌梗死面积百分比（P lt;0.05）。　结论　在心肌缺血的SD大鼠中，PolyHb可以有效的降低缺血再灌注损伤，从而达到心肌保护作用。
【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.

Citation： WAN Qin,BAO Min,LI Yi. Research on the Protective Effect of Polymerized Hemoglobin for Heart Muscles of Living Rats Undergoing Myocardial Ischemia-reperfusion. West China Medical Journal, 2011, 26(8): 1146-1149. doi: Copy

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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.

West China Medical Journal

Research on the Protective Effect of Polymerized Hemoglobin for Heart Muscles of Living Rats Undergoing Myocardial Ischemia-reperfusion

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