Yang Z P, Dettbarn W D
Department of Pharmacology and Neurology, Vanderbilt University, School of Medicine, Nashville, TN 37212, USA.
J Physiol Paris. 1998 Jun-Aug;92(3-4):157-61. doi: 10.1016/s0928-4257(98)80002-8.
A possible role of radical oxygen species (ROS) initiated lipid peroxidation in diisopropylphosphorofluoridate (DFP)-induced muscle necrosis was investigated by quantifying muscle changes in F2-isoprostanes, novel and extremely accurate markers of lipid peroxidation in vivo. A significant increase in F2-isoprostanes of 56% was found in the diaphragm of rats 60 min after DFP-induced fasciculations. As possible source of ROS initiating lipid peroxidation, the cytocrome-c oxidase (Cyt-ox) and xanthine dehydrogenase-xanthine oxidase (XD-XO) systems were investigated. Within 30 min of onset of fasciculations Cyt-ox activity was reduced by 50% from 0.526 to 0.263 mumol/mg prot/min and XO activity increased from 0.242 to 0.541 mumol/mg prot/min. Total XD-XO activity was unchanged, indicating a conversion from XD into XO. In rats pretreatment with the neuromuscular blocking agent d-tubocurarine, prevented DFP-induced fasciculations, increases in F2-isoprostanes and changes in Cyt-ox or XD-XO. The decrease in Cyt-ox and increase in XO suggest that ROS are produced during DFP induced muscle fasciculations initiating lipid peroxidation and subsequent myopathy.
通过量化F2-异前列腺素（体内脂质过氧化的新型且极其准确的标志物）的肌肉变化，研究了活性氧（ROS）引发的脂质过氧化在二异丙基氟磷酸酯（DFP）诱导的肌肉坏死中的可能作用。在DFP诱导肌束震颤后60分钟，大鼠膈肌中的F2-异前列腺素显著增加了56%。作为引发脂质过氧化的ROS的可能来源，研究了细胞色素c氧化酶（Cyt-ox）和黄嘌呤脱氢酶-黄嘌呤氧化酶（XD-XO）系统。在肌束震颤开始后的30分钟内，Cyt-ox活性从0.526μmol/mg蛋白/分钟降低了50%至0.263μmol/mg蛋白/分钟，XO活性从0.242μmol/mg蛋白/分钟增加至0.541μmol/mg蛋白/分钟。总XD-XO活性未改变，表明从XD转化为XO。在用神经肌肉阻滞剂d-筒箭毒碱预处理的大鼠中，可预防DFP诱导的肌束震颤、F2-异前列腺素增加以及Cyt-ox或XD-XO的变化。Cyt-ox的降低和XO的增加表明，在DFP诱导的肌肉肌束震颤过程中产生了ROS，引发了脂质过氧化和随后的肌病。
