McCutchan H J, Schwappach J R, Enquist E G, Walden D L, Terada L S, Reiss O K, Leff J A, Repine J E
Department of Orthopedics, University of Colorado Health Sciences Center, Denver 80262.
Am J Physiol. 1990 May;258(5 Pt 2):H1415-9. doi: 10.1152/ajpheart.1990.258.5.H1415.
We hypothesized that xanthine oxidase (XO)-derived hydrogen peroxide (H2O2) contributes to ischemic skeletal muscle injury during reperfusion. We found that after ischemia (3 h) and then reperfusion (4 h) rat gastrocnemius muscles had decreased contractile function following direct stimulation. Three lines of investigation suggested that XO-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle. First, treatment with dimethylthiurea (DMTU), a highly permeant O2 metabolite scavenger, but not urea, just before reperfusion improved muscle function in legs subjected to ischemia and then reperfusion. Second, gastrocnemius muscles from rats fed tungsten or allopurinol had negligible XO activities and increased muscle function after ischemia and reperfusion. Third, as assessed by measurement of skeletal muscle catalase activity in the presence of aminotriazole, H2O2 was measured during reperfusion of ischemic muscles from untreated or urea-treated rats but not during reperfusion of muscles from rats treated with DMTU, tungsten, or allopurinol.
我们推测，黄嘌呤氧化酶（XO）衍生的过氧化氢（H₂O₂）会导致再灌注期间缺血骨骼肌损伤。我们发现，在缺血（3小时）然后再灌注（4小时）后，直接刺激大鼠腓肠肌，其收缩功能下降。三项研究表明，XO衍生的H₂O₂会导致缺血骨骼肌的再灌注损伤。首先，在再灌注前用二甲基硫脲（DMTU，一种高渗透性的O₂代谢产物清除剂）而非尿素进行治疗，可改善经历缺血再灌注的腿部肌肉功能。其次，喂食钨或别嘌呤醇的大鼠的腓肠肌XO活性可忽略不计，且缺血再灌注后肌肉功能增强。第三，通过在氨基三唑存在下测量骨骼肌过氧化氢酶活性来评估，在未治疗或用尿素治疗的大鼠的缺血肌肉再灌注期间可检测到H₂O₂，但在用DMTU、钨或别嘌呤醇治疗的大鼠的肌肉再灌注期间未检测到。
