Amiloride和耗竭细胞内糖原对心肌缺血再灌注损伤的影响

本工作在离体大鼠等容收缩心脏模型上,观察在缺血前给予ａｍｉｌｏｒｉｄｅ和耗竭心肌细胞内糖原以减少Ｎａ＋－Ｈ＋交换的底物对缺血后再灌注损伤的影响,以探讨Ｎａ＋－Ｈ＋交换和Ｎａ＋－Ｃａ２＋交换机制在心肌缺血后再灌注损伤中的发病学意义。结果表明,Ａｍｉｌｏｒｉｄｅ及耗竭心肌细胞内糖原均能提高心脏血液动力学的恢复,心肌组织乳酸脱氢酶（ＬＤＨ）漏出及丙二醛（ＭＤＡ）生成减少,线粒体中谷胱甘肽过氧化物酶有较高的活性;心肌细胞内Ｎａ＋,Ｃａ２＋超负荷减轻。Ａｍｉｌｏｒｉｄｅ的心肌保护作用可能与其抑制再灌注初期的细胞膜Ｎａ＋－Ｈ＋交换机制有关。耗竭细胞内糖原因减少缺血末细胞内Ｈ＋的堆积,使Ｎａ＋－Ｈ＋交换底物减少而抑制Ｎａ＋－Ｈ＋交换机制。     

Na^＋—K^＋—ATP酶抑制与心肌缺血后再灌注性损伤

在离体大鼠心脏灌流模型上,观察细胞内高钠对心肌缺血后再灌注性损伤的影响。在低灌流过程中,给予Na~ -K~ -ATP酶抑制剂哇巴因造成细胞内高Na~ ,可加重缺血后再灌注心脏的血液动力学障碍;增加心肌组织丙二醛含量及冠脉流出液中乳酸脱氢酶的活性;降低线粒体及胞浆液中谷胱甘肽过氧化物酶活力;并使心肌组织中Ca~(2 )超负荷及K~ 丢失严重。因此,细胞内高Na~ 可能是心肌缺血后再灌注损伤的基础。     

激活细胞膜Na^＋／H^＋交换对心肌缺血再灌注损伤的影响

在离体大鼠等容收缩心脏灌流模型上,观察激活细胞膜Ｎａ＋／Ｈ＋交换对心肌缺血后再灌注性损伤的影响。采用经典ＮＨ４Ｃｌ负荷方法以激活细胞膜Ｎａ＋／Ｈ＋交换,结果表明,激活Ｎａ＋／Ｈ＋交换加重缺血后再灌注心脏血液动力学障碍,增加冠脉流出液中乳酸脱氢酶的活性,并使心肌组织中Ｎａ＋、Ｃａ２＋超负荷及Ｋ＋丢失加重。提示细胞膜Ｎａ＋／Ｈ＋交换是心肌缺血后再灌注损伤的发病机理之一。     

Na超负荷与Na/H交换的关系——在等容收缩离体大鼠心脏的研究

心脏富氧灌流30min稳定后随机分为四组:(1)对照组:富氧灌流75min;(2)低血流缺氧组:低血流缺氧45min后,再富氧灌流30min;(3)Ouabain组:于低血流缺氧过程中,溶Ouabain(200μmol/L)于K—H液中,余同组(2);(4)Ouabain+Amiloride组:除在低血流缺氧期给0.5mmol/L amiloride外,余同组(3)。与低血流缺氧组相比,Ouabain可引起再灌注时心肌Na的明显增加并伴有心室功能的抑制,Amiloride可明显减轻这一损害作用。这表明,Na/K ATPase活性的抑制与再灌注心肌的Na超载有关,而这一作用的机制可能是由于Na/H交换的激活所引起。     

Na超负荷与Na／H交换的关系—在等容收缩离体大鼠心脏...

Thirty min after stabilization perfusion with oxygenated buffer, hearts were divided in four groups: (1) Control group: 75 min. of aerobic perfusion; (2) Low flow anoxia group: 45 min. of low flow anoxic perfusion (95% N2:5%CO2, 0.15 ml/min.) followed by 30 min. of aerobic perfusion; (3) Ouabain group: protocol same as (2), except that ouabain (200 mumol/L) was added to anoxic perfusate during low flow anoxia; (4) Ouabain+Amiloride group: protocol same as (3) except that amiloride (0.5 mmol/I) was added to perfusate during low flow anoxia. Compared with the low flow anoxia group, ouabain resulted in an additional increase in Na during reperfusion accompanied with a depressed ventricular function. The deleterious effects of ouabain could be significantly combatted by amiloride. It is concluded that a decrease in Na/K ATPase activity may contribute to Na gain in reperfused myocardium, the mechanism of which might result from stimulation of Na/H exchange.