Marro Peter J, Mishra Om P, Delivoria-Papadopoulos Maria
Department of Pediatrics, Division of Neonatology, Barbara Bush Children's Hospital at Maine Medical Center, 22 Bramhall Street, Portland, ME 04102-3134, USA.
Brain Res. 2006 Feb 16;1073-1074:444-50. doi: 10.1016/j.brainres.2005.11.061. Epub 2006 Jan 26.
Adenosine, a purine nucleoside, is a potent inhibitory neuromodulator in the brain which may provide an important endogenous neuroprotective role during hypoxia-ischemia. Allopurinol, a xanthine oxidase inhibitor, blocks purine degradation and may result in the accumulation of purine metabolites, including adenosine, during hypoxia. The present study determines the effect of allopurinol administration prior to hypoxia on brain levels of adenosine and purine metabolites in the newborn piglet. Twenty-two newborn piglets (age 3-7 days) were studied: 5 untreated normoxic and 6 allopurinol-treated normoxic controls were compared to 5 untreated hypoxic and 6 allopurinol-treated hypoxic animals. Brain tissue energy metabolism was continuously monitored during hypoxia by (31)P NMR spectroscopy. Brain tissue levels of purines increased in both hypoxic groups during hypoxia, however, there were significantly higher increases in brain tissue levels of adenosine (66.5 +/- 30.5 vs. 19.4 +/- 10.7 nmol/gm), P < 0.01 and inosine (265 +/- 97.6 vs. 162.8 +/- 38.3 nmol/gm), P = 0.05 in the allopurinol-treated hypoxic group. Allopurinol inhibits purine degradation under severe hypoxic conditions and results in a significant increase in brain tissue levels of adenosine and inosine. The increased accumulation of CNS adenosine during hypoxia which is seen in the allopurinol-treated animals may potentiate adenosine's intrinsic neuroprotective mechanisms.
腺苷是一种嘌呤核苷，是大脑中一种强效的抑制性神经调质，在缺氧缺血期间可能发挥重要的内源性神经保护作用。别嘌醇是一种黄嘌呤氧化酶抑制剂，可阻断嘌呤降解，并可能在缺氧期间导致包括腺苷在内的嘌呤代谢产物积累。本研究确定了在缺氧前给予别嘌醇对新生仔猪大脑中腺苷和嘌呤代谢产物水平的影响。研究了22只新生仔猪（3 - 7日龄）：将5只未经处理的常氧仔猪和6只经别嘌醇处理的常氧对照仔猪与5只未经处理的缺氧仔猪和6只经别嘌醇处理的缺氧仔猪进行比较。在缺氧期间通过（31）P核磁共振波谱法持续监测脑组织能量代谢。缺氧期间，两个缺氧组的脑组织嘌呤水平均升高，然而，经别嘌醇处理的缺氧组脑组织腺苷水平（66.5±30.5对19.4±10.7 nmol/gm）显著升高，P < 0.01，肌苷水平（265±97.6对162.8±38.3 nmol/gm），P = 0.05。别嘌醇在严重缺氧条件下抑制嘌呤降解，导致脑组织腺苷和肌苷水平显著升高。在经别嘌醇处理的动物中，缺氧期间中枢神经系统腺苷积累增加可能会增强腺苷固有的神经保护机制。
