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肾缺血预处理减少心肌缺血-再灌注所致的心肌细胞凋亡

Renal ischemic preconditioning reduces cardiomyocytic apoptosis induced by myocardial ischemia-reperfusion

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【作者】 丁延峰张蔓蔓张爱子王义和何瑞荣

【Author】 DING Yan feng,ZHANG Man man,ZHANG Ai zi, et al (Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China)

【机构】 河北医科大学基础所生理室河北医科大学基础所组胚教研室河北医科大学基础所生理室 石家庄050017石家庄050017石家庄050017

【摘要】 在麻醉家兔心肌缺血 /再灌注 (myocardialischemia/reperfusion ,MIR)模型上 ,观察MIR和肾脏缺血预处理 (renalischemicpreconditioning ,RIP)对血流动力学、心外膜电图、心肌梗死范围、心肌细胞凋亡和凋亡相关调控基因蛋白(Fas、Bcl 2和Bax)的影响。所得结果如下 :(1)在MIR过程中 ,动脉血压、心率和心肌耗氧量呈进行性下降 ;心外膜电图ST段在缺血期明显抬高 ,再灌注时逐渐恢复至基础对照值。 (2 )MIR组的坏死心肌占缺血心肌的 (5 5 80±3 5 3) % ,RIP后心肌梗死范围降至 (36 5 1± 6 6 1) %。 (3)凝胶电泳显示 ,MIR组的缺血组织DNA呈云梯状 ,RIP +MIR组则无 ;原位末端标记表明 ,RIP中缺血未坏死心肌的凋亡细胞较MIR组稀少 ;流式细胞术测得MIR和RIP +MIR组中缺血心肌的细胞凋亡率分别为 (10 70± 1 80 ) %和 (5 86± 1 79) %。 (4 )在MIR和RIP +MIR组的缺血心肌中 ,Fas和Bax蛋白表达均明显增高 ,Bcl 2蛋白表达无明显变化。MIR组的Fas和Bax蛋白表达较RIP +MIR组的明显 ,MIR组中Bcl 2 /Bax较非缺血心肌组织和RIP +MIR组中的明显减小。以上结果表明 ,RIP减少MIR引发的心肌细胞凋亡 ,并可能通过减少MIR心肌组织中Fas和Bax蛋白的表达而起作用。

【Abstract】 The effects of myocardial ischemia reperfusion(MIR) and renal ischemic preconditioning (RIP) on hemodynamics, epicardial electrography, myocardial infarct size, cardiomyocytic apoptosis and gene proteins involving apoptosis (Fas, Bcl 2 and Bax) were observed in aneasthetized rabbit myocardium. The results are as following: (1) During MIR, heart rate,arterial blood pressure, and myocardial oxygen consumption were progressively decreased. The epicardial electrographic ST segment was significantly elevated during ischemia ( P <0.001) and returned to baseline during reperfusion. (2) The infarct size occupied (55.80±3.53)% of ischemic myocardium in MIR group while RIP reduced the infarct size to (36.51±6.61)%( P <0.01). (3) The cardiomyocytic apoptosis was observed in the transmission electron microscope. DNA ladder pattern of ischemic myocardium was revealed by agrose gel electrophoresis in MIR group while it was not found in RIP+MIR group. Apoptotic cardiomyocytes were sparse within ischemic myocardium at risk in RIP+MIR as compared with that in MIR heart. Apoptosis rates in ischemic myocardium from MIR and RIP+MIR group detected by flow cytometry was (10.70±1.80)% and (5.86±1.79)%( P <0.01), respectively. (4) Fas and Bax protein expressions in ischemic myocardium of MIR and RIP+MIR group were elevated as compared with those in non ischemic myocardium ( P <0.05). The Fas and Bax protein expression in MIR group was higher than that in RIP+MIR group ( P <0.05). Bcl 2/Bax ratio in MIR was lower than that in non ischemic myocardium and in RIP+MIR group ( P <0.01). It was suggested that RIP could decrease cardiomyocytic apoptosis induced by MIR and this action was mediated by the reduction of Fas and Bax protein expression.

【基金】 国家自然科学基金 (30 0 70 2 82 )
  • 【文献出处】 基础医学与临床 ,Basic Medical Sciences and Clinics , 编辑部邮箱 ,2001年06期
  • 【分类号】R363
  • 【被引频次】2
  • 【下载频次】66
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