缺氧缺血脑损伤时新生大鼠脑皮质神经细胞能量代谢的改变

Changes of energy metabol ism in the cortical neurons of newborn rats with cerebral hypoxia2ischemia

摘要:

目的 近年来的一些研究表明 ,线粒体能量代谢异常是新生儿缺氧缺血性脑病 (HIE)发病机制的重要环节之一。该实验研究新生大鼠缺氧缺血性脑损伤 (HIBD)时脑皮质神经细胞内磷酸肌酸 (PCr)、ATP和总腺苷酸池 (ATP +ADP +AMP)的变化。方法 7日龄Wistar大鼠随机分为假手术对照组 (n =6 )和HIBD组 (n =6 0 )。HIBD组新生鼠分别于缺氧缺血 (HI)后 0 ,2 ,4 ,6 ,8,1 0 ,1 2 ,2 4 ,4 8h和 72h断头 (每个时间点 6只 ) ,取左侧顶枕部脑皮质 ;假手术对照组新生鼠于假手术后 4h断头。用高效液相色谱方法检测脑皮质高能磷酸物质的含量。结果HIBD组新生鼠HI后 0hPCr,ATP和ATP +ADP +AMP即低于正常对照组 (P <0 .0 1或 0 .0 5 ) ,并于缺氧缺血后0～ 6h出现第 1次低谷 ,分别为对照组的 5 1 % ,71 % ,5 0 % ,缺氧缺血后 8～ 1 2h分别恢复到对照组的 92 % ,83%和83% ,与对照组比较差异无显著性 (P >0 .0 5 ) ;以后又下降到低于正常对照组 (P <0 .0 1 ) ,并于缺氧缺血后 2 4～4 8h下降到第 2次低谷 ,分别为对照组的 5 8% ,6 1 %和 32 %。结论 新生大鼠HIBD后 2 4～ 4 8h皮质神经细胞出现第 2次能量代谢衰竭 ,能量代谢变化可作为判断缺氧缺血性脑损伤干预手段是否有效的观察指标。

Abstract:

Energy metabolism of mitochondria plays an important role in hypoxic ischemic encephalopathy (HIE). This study aims to investigate the changes of energy metabolism following hypoxic ischemic brain damage (HIBD) in cortical neurons of newborn rats. Methods Seven day old Wistar rats were randomly assigned into a Sham operation control group (n=6) and a Cerebral hypoxia ischemia (HI) group. The HI group was divided into 10 subgroups of 6 animals, sacrificed respectively at 0, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hrs after HI. The rats in the Sham operation control group were sacrificed at 4 hrs post operatively. The concentrations of PCr, ATP, ADP and AMP in cortical neurons were measured with high performance liquid chromatography (HPLC). Results The concentrations of PCr, ATP and ATP+ADP+AMP decreased immediately after HI and reached a nadir 0-6 hrs after HI ( 51% , 71% and 50% of controls, respectively), returning almost to normal values by 8-12 hrs after HI. Twelve hrs after HI the values again decreased reaching a second nadir by 24-48 hrs post HI ( 58% , 61% , 33% of controls, respectively; P< 0.05 ). Conclusions There is a secondary decrease in high energy phosphates 24-48 hrs after cerebral HI in newborn rats. Changes of energy metabolism may serve as indicators in evaluating the efficacy of intervention for HIBD.