Okabe H
Department of Internal Medicine (II), Jikei University School of Medicine, Tokyo, Japan.
Nihon Jinzo Gakkai Shi. 1996 Dec;38(12):577-84.
Xanthine dehydrogenase (XDH) and xanthine oxidase (XO) are enzymes involved in the metabolism of purines in various organisms. XO produces superoxide radicals, suggesting that is responsible for tissue ischemia-reperfusion injury. To test this notion further studies were performed on rat kidneys and the time course of changes in purine nucleotides, oxypurines and XDH and XO activity was determined. At 24 hours after reperfusion subsequent to 30-minute ischemia, serum creatinine increased to 0.83 +/- 0.74 mg/dl from 0.28 +/- 0.06 mg/dl (the level prior to ischemia, the control). Renal ATP and ADP contents were reduced after ischemia lasting for 30 minutes and restored 10 minutes after reperfusion following 30 minutes of ischemia. The renal AMP content increased after 30 minutes of ischemia and recovered within 10 minutes after reperfusion. The total adenine nucleotide (TAN) content was reduced gradually during ischemia-reperfusion in the rat kidney. Although the energy charge was reduced following 30 minutes of ischemia, it was restored to the control level 10 minutes following reperfusion. Hypoxanthine (HX) and xanthine (X), which had accumulated at 30 minutes after ischemia, were reduced to the control levels 10 minutes after reperfusion. There were no significant changes in the pre-ischemia values of total XDH and XO activities or XDH/XO ratio during the period nor at various time intervals (up to 24 hours) during reperfusion. It was shown that HX and X accumulate without significant conversion of XDH to XO during ischemia. Therefore the putative role of XO in ischemia-reperfusion injury seems to more complex than initially predicted.
黄嘌呤脱氢酶(XDH)和黄嘌呤氧化酶(XO)是参与多种生物体嘌呤代谢的酶。XO会产生超氧自由基,这表明它与组织缺血再灌注损伤有关。为了进一步验证这一观点,对大鼠肾脏进行了研究,并测定了嘌呤核苷酸、氧嘌呤以及XDH和XO活性的变化时间进程。在30分钟缺血后的再灌注24小时时,血清肌酐从0.28±0.06mg/dl(缺血前的对照水平)升至0.83±0.74mg/dl。持续30分钟缺血后,肾脏ATP和ADP含量降低,在30分钟缺血后的再灌注10分钟时恢复。缺血30分钟后肾脏AMP含量增加,并在再灌注后10分钟内恢复。大鼠肾脏在缺血再灌注过程中总腺嘌呤核苷酸(TAN)含量逐渐降低。虽然缺血30分钟后能量电荷降低,但在再灌注10分钟后恢复到对照水平。缺血30分钟时积累的次黄嘌呤(HX)和黄嘌呤(X)在再灌注10分钟后降至对照水平。在该时间段内以及再灌注期间(长达24小时)的各个时间间隔,缺血前总XDH和XO活性或XDH/XO比值均无显著变化。结果表明,在缺血过程中HX和X积累,而XDH没有明显转化为XO。因此,XO在缺血再灌注损伤中的假定作用似乎比最初预测的更为复杂。