Superoxide scavengers augment contractile but not energetic responses to hypoxia in rat diaphragm.
Superoxide scavengers augment contractile but not energetic responses to hypoxia in rat diaphragm.
复制标题
超氧化物清除剂增强大鼠膈肌对缺氧的收缩反应，但不增强能量反应。
DOI：
10.1152/japplphysiol.01022.2004
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Clanton,TL
中科院分区：
文献类型：
--
作者：
Wright,VP;Klawitter,PF;Iscru,DF;Merola,AJ;Clanton,TL
急性严重缺氧会抑制收缩功能并诱发骨骼肌的适应，但目前我们对此还只是部分了解。先前的研究表明，缺氧期间给予的抗氧化剂（AOX）可以部分保护收缩功能，但这并不是一个普遍的发现。这项研究证实，特定的 AOX（主要作为超氧化物清除剂）可以在严重缺氧时保护收缩功能。此外，还测试了保护机制涉及高能磷酸盐（ATP、磷酸肌酸）的保存和 Pi 的还原的假设。大鼠膈肌条用 AOX 处理并进行 30 分钟的缺氧。通过使用抽搐和强直刺激以及缺氧（挛缩）期间发生的被动力的升高程度来检查收缩功能。在 30 分钟缺氧暴露结束时测量高能磷酸盐。用超氧化物清除剂 4,5-二羟基-1,3-苯二磺酸（Tiron，10 mM）或五氯化锰（III）四（1-甲基-4-吡啶基）卟啉（50 μM）处理可抑制缺氧期间的挛缩并保护最大强直力。N-乙酰半胱氨酸（10 或 18 mM）对强直力的产生没有影响。没有 AOX 的缺氧期间的挛缩也被证明取决于细胞外 Ca2+ 浓度。尽管缺氧仅导致 ATP 浓度小幅下降，但磷酸肌酸浓度下降至对照的 10%。在缺氧期间，AOX 处理对高能磷酸盐没有一致的影响。结果表明，超氧化物清除剂可以通过不涉及高能磷酸盐保存的机制来保护收缩功能并减少缺氧时的挛缩。
Acute exposure to severe hypoxia depresses contractile function and induces adaptations in skeletal muscle that are only partially understood. Previous studies have demonstrated that antioxidants (AOXs) given during hypoxia partially protect contractile function, but this has not been a universal finding. This study confirms that specific AOXs, known to act primarily as superoxide scavengers, protect contractile function in severe hypoxia. Furthermore, the hypothesis is tested that the mechanism of protection involves preservation of high-energy phosphates (ATP, creatine phosphate) and reductions of Pi. Rat diaphragm muscle strips were treated with AOXs and subjected to 30 min of hypoxia. Contractile function was examined by using twitch and tetanic stimulations and the degree of elevation in passive force occurring during hypoxia (contracture). High-energy phosphates were measured at the end of 30-min hypoxia exposure. Treatment with the superoxide scavengers 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron, 10 mM) or Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride (50 μM) suppressed contracture during hypoxia and protected maximum tetanic force.N-acetylcysteine (10 or 18 mM) had no influence on tetanic force production. Contracture during hypoxia without AOXs was also shown to be dependent on the extracellular Ca2+concentration. Although hypoxia resulted in only small reductions in ATP concentration, creatine phosphate concentration was decreased to ∼10% of control. There were no consistent influences of the AOX treatments on high-energy phosphates during hypoxia. The results demonstrate that superoxide scavengers can protect contractile function and reduce contracture in hypoxia through a mechanism that does not involve preservation of high-energy phosphates.