高翔;高全;李涛;陆德琴;
GAO Xiang,GAO Quan,LI Tao,LU Deqin(1.Department of Pathophysiology,Guiyang Medical College,Guiyang 550004;2.Staff and Workers' Hospital Attached to Guiyang Xin Tian Photoelectric Science and Technology Limited Company,Guiyang 550018)

• 1:贵阳医学院病理生理学教研室
• 2:贵阳新天光电科技有限公司职工医院
• 3:贵阳医学院病理生理学教研室
• 4:贵阳医学院病理生理学教研室 贵州贵阳550004

摘要(Abstract)：

目的:探讨线粒体ATP敏感性钾通道(mitoKATP)是否参与葛根素(puerarin,PUE)预处理保护心肌缺血再灌注损伤的机制。方法:开胸结扎左冠状动脉前降支(LAD),复制大鼠心肌缺血再灌注损伤模型,设立假手术(sham)组、缺血再灌注(I/R)组、PUE预处理组,PUE预处理加mitoKATP特异性阻断剂5-hydroxydecanoate(5-HD)组和5-HD组,采用TTC法测定心肌梗塞面积,TUNEL法检测心肌细胞凋亡情况,并测定血清肌酸激酶(CK)活力。结果:I/R组较sham组心肌梗塞面积、血清CK活力以及心肌细胞凋亡指数显著增高;与I/R组比较,PUE预处理组心肌梗塞面积明显缩小,血清CK活力和心肌细胞凋亡指数显著降低;PUE加5-HD组与PUE预处理组相比心肌梗塞面积增大,心肌细胞凋亡增加,血清CK活力增高;5-HD组与I/R组相比以上指标差异均无显著意义。结论:葛根素预处理明显减轻了大鼠心肌I/R损伤,其心肌保护效应可能部分通过开放mitoKATP通道的途径产生。
Objective:To investigate the role of mitochondrial KATP channel(mitoKATP) in the protective effect of puerarin(PUE) on myocardial ischemia-reperfusion injury in rats.Methods: Rat heart ischemia-reperfusion injury(I/R) models were induced by occluding the left anterior descending coronary artery for 45 min and reperfusion for 120 min.Fifty-five rats were randomly divided into five groups(11 in each):(1) Group sham(did not receive operation);(2) group I/R;(3) group PUE(received PUE at a dose of 100 mg/kg intravenously 5 min before ischemia);(4) group P5D(received 5-hydroxydecanoate,a mitoKATP specific inhibitor,at a dose of 5 mg/kg intravenously 15 min before ischemia and PUE treatment at 5 min before ischemia);and(5) group 5-HD(received 5-hydroxydecanoate alone 15 minutes before ischemia).TTC dyeing was used to determine the myocardial infarction size.Cardiac myocytes apoptosis was detected by using TUNEL.Creatine kinase activity(CK) in serum was measured simultaneously.Results: Infarct size,cardiomyocytes apoptosis and CK activity in serum of group I/R were obviously higher than those in group sham(P<0.05 or P<0.01).Compared with group I/R,all these parameters in PUE groups were significantly lower(P<0.05 or P<0.01).While,in group P5D,all these parameters were significantly higher than those in group PUE.There was no significant difference found among the parameters of groups P5D,I/R and 5-HD.Conclusions: Preconditioning with puerarin can significantly reduce myocardial ischemia-reperfusion injury in rats.The protective effect of puerarin to myocardium is partly via opening the mitoKATP channel.

关键词(KeyWords)： 心肌再灌注损伤;心肌缺血;心肌梗塞;大鼠,Wistar;葛根素;线粒体ATP敏感性钾通道
myocardial reperfusion injury;myocardial ischemia;myocardial infarction;rats, Wistar;puerarin;mitochondrial KATP channel

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 高翔;高全;李涛;陆德琴;
GAO Xiang,GAO Quan,LI Tao,LU Deqin(1.Department of Pathophysiology,Guiyang Medical College,Guiyang 550004;2.Staff and Workers' Hospital Attached to Guiyang Xin Tian Photoelectric Science and Technology Limited Company,Guiyang 550018)

Email:

DOI: 10.19367/j.cnki.1000-2707.2007.01.012

参考文献(References)：

• [1]Dos Santos P,Kowaltowski AJ,Laclau MN,et al.Mecha-nisms by which opening the mitochondrial ATP-sensitive K(+)channel protects the ischemic heart[J].Am J Phys-iol Heart Circ Physiol,2002,283(1):H284-295.
• [2]Wang Y,Kudo M,Xu M,et al.Mitochondrial K(ATP)channel as an end effector of cardioprotection during latepreconditioning:triggering role of nitric oxide[J].J MolCell Cardiol,2001,33(11):2037-2046.
• [3]黄漫翔.葛根素对心血管系统作用的研究进展[J].广东药学,2000(2):9-11.
• [4]郭鹞.人类疾病的动物模型[M].北京:人民卫生出版社,1982,365-367.
• [5]覃数,陈运贞,王志华.大白鼠实验性心肌缺血再灌注模型制备与心电图改变的特点[J].重庆医科大学学报,1998,23(1):8-11.
• [6]Noma A.ATP-regulated K+channels in cardiac muscle[J].Nature,1983,305(5930):147-148.
• [7]Fryeer RM,Eells JT,Hsu AK,et al.Ischemic precondi-tioning in rats:role of mitochondrial KATPchannel in pres-ervation pf mitochondrial function[J].Am J Physiol HeartCirc Physiol,2000,278(1):H305-312.
• [8]刘蔚,汪海.抗心肌缺血药物的新靶点:线粒体ATP敏感性钾通道[J].中国药理学通报,2001(6):610-613.
• [9]刘晨,祝宝华,奚群莫.mitoKATP和肌浆网钙ATP酶在心肌缺血预适应的作用及机制[J].实用临床医药杂志,2005(3):25-27.
• [10]张远荣,蒋企洲.葛根素的抗氧化活性作用[J].实用临床医药杂志,2005(5):92-93.
• [11]刘琦,常志文,卢玲巧,等.葛根素对心肌缺血再灌注损伤的影响[J].中国药学杂志,2000,35(9):642.
• [12]孙云翔.葛根素扩血管作用及其机制初探[J].中草药,2003(8):733-734.
• [13]陈江斌,黄从新,李庚山,等.葛根素对再灌注损伤心肌细胞内K+/Na+及Ca2+浓度的影响[J].中国危重病急救医学,1999,11(1):48-49.

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