Maulik D, Zanelli S, Numagami Y, Ohnishi S T, Mishra O P, Delivoria-Papadopoulos M
Department of Obstetrics and Gynecology, Winthrop-University Hospital, 259 First Street, Mineola, NY 11501, USA.
Brain Res. 1999 Jan 30;817(1-2):117-22. doi: 10.1016/s0006-8993(98)01235-9.
Previous studies have shown, employing direct measurements with electron spin resonance (ESR) spectroscopy, that hypoxia induces an increased production of oxygen free radicals (OFR) in the brain of the guinea pig fetus. The present study using the same approach, investigated the effects of maturity and Mg2+-pretreatment on hypoxia-induced OFR formation in the guinea pig fetal brain. The normoxic and the hypoxic groups were exposed for 60 min to 21% or 7% oxygen, respectively. The control group consisted of term fetuses exposed to normoxia (n=7) and hypoxia (n=7). The experimental groups consisted of the following: (a) for the investigation on maturity effect, preterm fetuses (40 days) exposed to normoxia (n=6) or hypoxia (n=6); and (b) for the Mg2+-pretreatment investigation, term fetuses (60 days) exposed to normoxia (n=6) or hypoxia (n=6) following maternal pretreatment with Mg2+ which consisted of an initial bolus of MgSO4 (600 mg/kg, i.p.) 1 h prior to hypoxia followed by a second dose (300 mg/kg, i.p.). Oxygen free radicals were measured by ESR spectroscopy in the fetal cerebral cortical tissue utilizing phenyl-N-tert-butylnitrone (PBN) spin trapping. Fetal brain tissue hypoxia was documented biochemically by decreased tissue levels of ATP and phosphocreatine. In the control group of term fetuses, the cortical tissue from hypoxic fetuses showed a significant increase in spin adducts (71% increase, p<0.01). In the preterm group, the cortical tissue from hypoxic fetuses showed a 33% increase in spin adducts (p<0.001). The baseline free radical generation during normoxia was 22.5% higher at preterm than at term (41.4+/-3.5 units/g issue vs. 33.8+/-9.3 units/g tissue, p<0.05). In Mg2+-treated groups, spin adduct levels in cortical tissue from hypoxic fetuses did not significantly differ from those of the normoxic group (30.2+/-9.9 units/g tissue, normoxic-Mg2+ vs. 30. 6+/-8.1 units/g tissue, hypoxic-Mg2+). The results indicate that the fetal brain at term may be more susceptible to hypoxia-induced free radical damage than at preterm and that Mg2+ administration significantly decreased the hypoxia-induced increase in oxygen free radical generation in the term fetal guinea pig brain in comparison with non-treated hypoxic group.
以往的研究采用电子自旋共振（ESR）光谱直接测量法表明，缺氧会导致豚鼠胎儿大脑中氧自由基（OFR）的生成增加。本研究采用相同方法，调查了成熟度和镁离子预处理对豚鼠胎儿大脑中缺氧诱导的OFR形成的影响。常氧组和缺氧组分别暴露于21%或7%的氧气中60分钟。对照组由足月胎儿组成，分别暴露于常氧（n = 7）和缺氧（n = 7）环境。实验组如下：（a）为研究成熟度的影响，早产胎儿（40天）暴露于常氧（n = 6）或缺氧（n = 6）环境；（b）为研究镁离子预处理的影响，足月胎儿（60天）在母体用镁离子预处理后暴露于常氧（n = 6）或缺氧（n = 6）环境，镁离子预处理包括在缺氧前1小时静脉注射硫酸镁初始剂量（600 mg/kg，腹腔注射），随后再注射一次剂量（300 mg/kg，腹腔注射）。利用苯基 - N - 叔丁基硝酮（PBN）自旋捕获技术，通过ESR光谱测量胎儿大脑皮质组织中的氧自由基。通过检测组织中ATP和磷酸肌酸水平降低，生化记录胎儿脑组织缺氧情况。在足月胎儿对照组中，缺氧胎儿的皮质组织自旋加合物显著增加（增加71%，p < 0.01）。在早产组中，缺氧胎儿的皮质组织自旋加合物增加33%（p < 0.001）。早产时正常氧分压下的基线自由基生成比足月时高22.5%（41.4±3.5单位/克组织 vs. 33.8±9.3单位/克组织，p < 0.05）。在镁离子处理组中，缺氧胎儿皮质组织中的自旋加合物水平与常氧组无显著差异（常氧 - 镁离子组为30.2±9.9单位/克组织，缺氧 - 镁离子组为30.6±8.1单位/克组织）。结果表明，足月胎儿大脑可能比早产胎儿大脑更容易受到缺氧诱导的自由基损伤，并且与未处理的缺氧组相比，给予镁离子可显著降低足月豚鼠胎儿大脑中缺氧诱导的氧自由基生成增加。
