Uludag University Medical School, Department of Pharmacology, Turkey.
Neurosci Lett. 2013 May 10;542:65-70. doi: 10.1016/j.neulet.2013.02.035. Epub 2013 Feb 28.
Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neurological disability requiring newer therapeutic strategies. Uridine is the principal circulating pyrimidine in humans and a substrate for nucleotides and membrane phospholipids. The objective of this study was to investigate the effects of uridine in a neonatal rat model of HIE. Rat pups subjected to hypoxic-ischemic insult on postnatal day 7 were injected intraperitoneally with either saline or uridine (100, 300 or 500mg/kg) for three consecutive days and brains were collected for evaluation of brain infarct volume and apoptosis. Compared with Control group, uridine at 300 and 500mg/kg doses significantly reduced percent infarct volume, TUNEL(+) cell ratio and active Caspase-3 immunoreactivity in the cortex, as well as in CA1 and CA3 regions of the hippocampus. Uridine (300 and 500mg/kg) also decreased active Caspase-3 expression in the ipsilateral hemisphere. These data indicate that uridine dose-dependently reduces brain injury in a rat model of neonatal HIE by decreasing apoptosis.
新生儿缺氧缺血性脑病（HIE）是一种需要新的治疗策略的主要神经功能障碍。尿苷是人类主要的循环嘧啶核苷，也是核苷酸和膜磷脂的底物。本研究旨在探讨尿苷在新生大鼠 HIE 模型中的作用。将 7 日龄新生大鼠置于缺氧缺血环境中，然后连续 3 天腹腔内注射生理盐水或尿苷（100、300 或 500mg/kg），并收集大脑评估脑梗死体积和细胞凋亡。与对照组相比，300mg/kg 和 500mg/kg 剂量的尿苷可显著降低皮质、海马 CA1 和 CA3 区的梗死体积百分比、TUNEL（+）细胞比率和活性 Caspase-3 免疫反应性。尿苷（300 和 500mg/kg）还降低了对侧半球的活性 Caspase-3 表达。这些数据表明，尿苷通过减少细胞凋亡，剂量依赖性地降低了新生大鼠缺氧缺血性脑病模型中的脑损伤。
