Levy Roni, Glozman Sabina, Milman Dora, Seruty Catherine, Hagay Zion, Yavin Ephraim, Groner Yoram
Department of Obstetrics and Gynecology, Kaplan Medical Center, Weizmann Institute, Rehovot, Israel.
J Perinat Med. 2002;30(2):158-65. doi: 10.1515/JPM.2002.020.
To examine the effect of overexpression of human intracellular copper-zinc superoxide dismutase (CuZnSOD1) gene on fetal mice brain exposed to in-utero ischemic reperfusion injury.
Transient in-utero ischemia (7 min) was induced in pregnant transgenic mice overexpressing human CuZnSOD1 and wild-type mice by occluding the blood supply to the uterine artery on day 17 of pregnancy, followed by 24 hours of reperfusion. The level of lipid peroxidation in fetal mice brains was compared between the transgenic and non-transgenic (control) fetal mice. Motor and coordination skills of transgenic and control adult mice (six to eight months old) which were exposed to ischemic reperfusion injury in-utero were compared by the rope grip test and visible platform task.
We first measured CuZnSOD1 activity in the brains of the transgenic fetal mice and confirmed that the enzyme activity is 4.2-fold higher than control. We also established that ischemia reperfusion on day 17 of pregnancy led to increased level of TBARS (Thiobarbituric acid reactive substance) in brains of wild-type fetal mice when compared to sham operated mice (72.5 +/- 3.4 vs. 49.4 +/- 1.5 nmol/mg. p < 0.001). The increase was markedly accentuated in the CuZnSOD1 transgenic mice, and significantly higher compared to control mice exposed to ischemia-reperfusion (85.6 +/- 4.0 vs. 69.5 +/- 2.3 nmol/mg, p < 0.001). Moreover, we found that the transgenic mice that were subjected to in-utero ischemia reperfusion exhibited a significantly higher rate of failures in the rope grip test and poorer performance in the visible platform task, when compared to non-transgenic mice exposed to identical insult.
Oxygen free radicals play an important role in the pathogenesis of perinatal hypoxia. Overexpression of the enzyme CuZnSOD1 in transgenic mice exposed their brains to increased damage during ischemic-reperfusion insult.
研究人细胞内铜锌超氧化物歧化酶（CuZnSOD1）基因过表达对宫内缺血再灌注损伤的胎鼠脑的影响。
在妊娠第17天，通过阻断子宫动脉血供，对过表达人CuZnSOD1的转基因妊娠小鼠和野生型小鼠进行短暂宫内缺血（7分钟），随后再灌注24小时。比较转基因和非转基因（对照）胎鼠脑内脂质过氧化水平。通过握力试验和可视平台任务比较宫内暴露于缺血再灌注损伤的转基因和对照成年小鼠（6至8个月大）的运动和协调能力。
我们首先测量了转基因胎鼠脑内的CuZnSOD1活性，证实该酶活性比对照高4.2倍。我们还确定，与假手术小鼠相比，妊娠第17天的缺血再灌注导致野生型胎鼠脑内硫代巴比妥酸反应物质（TBARS）水平升高（72.5±3.4对49.4±1.5 nmol/mg，p<0.001）。在CuZnSOD1转基因小鼠中，这种升高明显加剧，与暴露于缺血再灌注的对照小鼠相比显著更高（85.6±4.0对69.5±2.3 nmol/mg，p<0.001）。此外，我们发现，与暴露于相同损伤的非转基因小鼠相比，宫内经历缺血再灌注的转基因小鼠在握力试验中的失败率显著更高，在可视平台任务中的表现更差。
氧自由基在围产期缺氧的发病机制中起重要作用。转基因小鼠中CuZnSOD1酶的过表达使其脑在缺血再灌注损伤期间受到更大损伤。
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