Linas S L, Whittenburg D, Repine J E
University of Colorado School of Medicine, Webb-Waring Lung Institute, Denver General Hospital 80204-4507.
Am J Physiol. 1990 Mar;258(3 Pt 2):F711-6. doi: 10.1152/ajprenal.1990.258.3.F711.
Oxygen metabolites formed during reperfusion of ischemic kidneys prevent recovery of renal function after short periods of renal ischemia. Xanthine oxidase has been proposed as a source of toxic oxygen metabolites during reperfusion of ischemic kidneys. To determine whether the enzyme is converted from the non-oxygen metabolite-producing dehydrogenase (type D) to the oxygen metabolite-producing oxidase (type O), we measured type D and type O (total, reversible, and irreversible) xanthine oxidase in renal cortical homogenates after 30 min of ischemia in vivo and 60 min of reperfusion by the isolated perfused kidney technique. Total enzyme activity (type D plus type O) was not altered by ischemia or reperfusion. Compared with nonischemic conditions, ischemia increased total type O (53 +/- 5 vs. 21 +/- 3%, P less than 0.01) and reversible type O (15.4 +/- 1.5 vs. 2.1 +/- 1.4 U/g) xanthine oxidase activities. Reperfusion further increased total type O (82 +/- 3%) and reversible type O (27.7 +/- 3.3 U/g, both P less than 0.01 vs. nonischemic perfusions) xanthine oxidase activities. To determine the physiological role of xanthine oxidase in renal ischemia, we depleted rats of xanthine oxidase by feeding tungsten. After 4 wk of tungsten, renal xanthine oxidase levels were reduced by greater than 90% and renal function was markedly improved during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
缺血性肾脏再灌注过程中形成的氧代谢产物会阻碍肾脏在短时间缺血后恢复功能。黄嘌呤氧化酶被认为是缺血性肾脏再灌注过程中有毒氧代谢产物的来源。为了确定该酶是否从不产生氧代谢产物的脱氢酶（D型）转化为产生氧代谢产物的氧化酶（O型），我们通过离体灌注肾脏技术，在体内缺血30分钟和再灌注60分钟后，测量了肾皮质匀浆中D型和O型（总、可逆和不可逆）黄嘌呤氧化酶的含量。总酶活性（D型加O型）不受缺血或再灌注的影响。与非缺血状态相比，缺血增加了总O型（53±5%对21±3%，P<0.01）和可逆O型（15.4±1.5对2.1±1.4 U/g）黄嘌呤氧化酶活性。再灌注进一步增加了总O型（82±3%）和可逆O型（27.7±3.3 U/g，与非缺血灌注相比，P均<0.01）黄嘌呤氧化酶活性。为了确定黄嘌呤氧化酶在肾脏缺血中的生理作用，我们通过喂食钨来使大鼠体内的黄嘌呤氧化酶缺失。在喂食钨4周后，肾脏黄嘌呤氧化酶水平降低了90%以上，并且在再灌注期间肾功能明显改善。（摘要截短至250字）
