Marro P J, McGowan J E, Razdan B, Mishra O P, Delivoria-Papadopoulos M
Department of Pediatrics, Maine Medical Center, Portland 04102.
Brain Res. 1994 Jul 4;650(1):9-15. doi: 10.1016/0006-8993(94)90200-3.
Oxygen-free radicals generated by xanthine oxidase during hypoxia-ischemia may result in cellular injury through harmful effects on membrane phospholipids. The present study investigated the effect of administration of allopurinol, an inhibitor of xanthine oxidase, on free-radical generation and brain cell membrane injury during hypoxia by inhibiting the breakdown of hypoxanthine to uric acid. Brain cell membrane Na+,K(+)-ATPase activity and lipid peroxidation products (conjugated dienes and fluorescent compounds) were determined as indices of brain membrane function and structure. Cerebral oxygenation was continuously monitored during hypoxia by 31P-NMR spectroscopy. Plasma and brain tissue levels of uric acid were measured to evaluate xanthine oxidase activity and purine degradation. Na+,K(+)-ATPase activity decreased significantly in both hypoxic groups; however, the allopurinol-treated hypoxic group showed a smaller decrease than the untreated hypoxic group (47.3 +/- 4.9 vs. 42.0 +/- 2.7 mumol Pi/mg protein/h, P < 0.05), respectively. Conjugated dienes increased significantly in the untreated hypoxic compared to control animals (0.070 +/- 0.045 vs. 0.004 +/- 0.006 mumol/g brain, P < 0.05), with the allopurinol-treated animals having intermediate values (0.053 +/- 0.039 mumol/g brain). Fluorescent compounds were lower in the allopurinol-treated hypoxic group compared to the untreated hypoxic group (0.79 +/- 0.19 vs. 1.06 +/- 0.60 micrograms/quinine sulfate/g brain, P < 0.05). Measurements of serum and brain tissue uric acid were significantly lower during hypoxia in the allopurinol-treated compared to the untreated group (30.3 +/- 15.6 vs. 45.7 +/- 10.6 microM (P < 0.05) and 1.69 +/- 0.97 vs. 4.27 +/- 2.37 nmol/g (P < 0.05), respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
缺氧缺血期间黄嘌呤氧化酶产生的氧自由基可能通过对膜磷脂的有害作用导致细胞损伤。本研究通过抑制次黄嘌呤分解为尿酸，研究了黄嘌呤氧化酶抑制剂别嘌呤醇的给药对缺氧期间自由基产生和脑细胞膜损伤的影响。测定脑细胞膜Na +，K（+）-ATP酶活性和脂质过氧化产物（共轭二烯和荧光化合物）作为脑膜功能和结构的指标。在缺氧期间通过31P-NMR光谱连续监测脑氧合。测量血浆和脑组织中的尿酸水平以评估黄嘌呤氧化酶活性和嘌呤降解。两个缺氧组的Na +，K（+）-ATP酶活性均显著降低；然而，别嘌呤醇治疗的缺氧组的降低幅度小于未治疗的缺氧组（分别为47.3±4.9对42.0±2.7μmolPi / mg蛋白/小时，P <0.05）。与对照动物相比，未治疗的缺氧组中共轭二烯显著增加（0.070±0.045对0.004±0.006μmol/ g脑，P <0.05），别嘌呤醇治疗的动物具有中间值（0.053±0.039μmol/ g脑）。与未治疗的缺氧组相比，别嘌呤醇治疗的缺氧组中的荧光化合物含量较低（0.79±0.19对1.06±0.60微克/硫酸奎宁/ g脑，P <0.05）。与未治疗组相比，别嘌呤醇治疗组在缺氧期间血清和脑组织尿酸的测量值显著降低（分别为30.3±15.6对45.7±10.6μM（P <0.05）和1.69±0.97对4.27±2.37 nmol / g（P <0.05））。（摘要截短为250字）
