关闭线粒体通透性转变孔对未成熟兔缺血心肌的保护作用  

Protective Effects of Closing Mitochondrial Permeability Transition Pore on Ischemic Myocardium in Immature Rabbits

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作  者:范勇[1] 林茹[1] 

机构地区:[1]浙江大学医学院附属儿童医院,浙江杭州310003

出  处:《浙江预防医学》2008年第10期5-7,共3页Zhejiang Journal of Preventive Medicine

摘  要:目的本实验旨在观察及了解线粒体通透性转变孔(MPTP)抑制剂和钾离子通道(KATP)开放剂对未成熟兔缺血心肌的保护作用及两者间的作用关系。方法未成熟大耳白幼兔45只,体重350~450g,年龄3~4W。随机分为5组,均取离体心脏悬挂于改良Langendorff灌流装置,K-H液平衡20min后,各组灌注含不同成分的停搏液,各组均30min重复灌注一次停搏液,每次20ml,共灌注2次。心脏置于36±1℃恒温器中,缺血60min,再K-H液灌注60min。5组灌注的停搏液分别为St.Thomas(10只);St.Thomas+30μmol/Ldiazoxide(8只);St.Thomas+0.2μmol/L cyclosporin A(10只);St.Thomas+30μmol/L diazoxide+20μmol/Latractyloside(8只);St.Thomas+30μmol/L diazoxide+100μmol/L 5-hydroxydecanoic acid(9只)。其中St.Thomas+cyclosporin A组和St.Thomas+diazoxide+atractyloside组在缺血60min后先分别给含有0.2μmol/L cyclosporin A或20μmol/L atractyloside的K-H液复灌10min,然后继续给K-H液灌注50min。结果再灌注后经特异性KATP开放剂diazoxide或特异性MPTP抑制剂cyclosporin A强化的St.Thomas停搏液组与St.Thomas组比较,可显著促进未成熟兔缺血心肌的功能恢复,冠脉流量恢复率增加明显(P〈0.05),而特异性MPTP开放剂atractyloside可阻断它们的效应(P〈0.05)。特异性KATP阻滞剂5-HD也可阻断diazoxide的效应(P〈0.05)。结论ATP钾离子通道开放剂和线粒体通透性转变孔抑制剂均对未成熟缺血心肌有明显的保护作用,且ATP钾离子通道开放剂很可能是通过关闭线粒体通透性转变孔来起到心肌保护作用的。Objective To observe the protective effects of mitochondrial permeability transition pore inhibitor and potassium channel openers on isehemie myocardium in immature rabbits as well as their action relation. Methods 45 immature rabbits, 3-4 weeks old, 350-450 grams, were randomized to five groups. After control perfusion in modified Langendorff mode with Krebs-Henseleit bicarbonate buffer for 20 minutes, the isolated immature rabbit hearts were infused twice with 20 ml of different cardioplegia respectively every 30 minutes. The hearts were persevered in 36± 1℃ for one hour, then were reperfused with Krebs-Henscleit bicarbonate buffer for 60 minutes. The different cardioplegia including St. Thomas (10 rabbits), St. Thomas + 30μmol/L diazoxide (8 rabbits), St. Thomas + 0.2/anol/L cyclospofine A ( 10 rabbits), St. Thomas + 30μmol/L diazoxide + 20μmol/L atractyloside (8 rabbits) and St. Thomas + 30μmol/L diazoxide + 100μmol/L 5-hydorxydecanoic acid (9 rabbits) were set up for the five groups respectively. The hearts of St. Thomas + cyclosporine and St. Thomas + diazoxide + atractyleside groups were reperfused with Krebs-Henseleit bicarbonate buffer containing 0.2μmol/L cyclosporine A or 20μmol/L atractyloside for 10 minutes firstly, then with Krebs-Henseleit bicarbonate buffer for the later 50 minutes. The hemodynamie parameters and coronary flow were measured before ischemia and repeffusion. Results After reperfusion, compared with hyperkalemic cardioplegic solution, hyperkalemic cardioplegie solution containing potassium channel openers diazoxlde or mitochendrial permeability transition pore inhibitor cyclosporine A improved the recovery of cardiac function and coronary flow significantly (p 〈 0.05). However, mitochondrial permeability transition pore openers atractyloside attenuated their effects (p 〈 0.05) as well as potassium channel inhibitor 5-HD (p 〈 0.05). Conclusion Both potassium channel openers diazoxide and mitochondrial permeability tr

关 键 词:线粒体通透性转变孔 未成熟兔 心肌保护 

分 类 号:R332[医药卫生—人体生理学]

 

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