Neuroprotective effects of volume-regulated anion channel blocker DCPIB on neonatal hypoxic-ischemic injury

Neuroprotective effects of volume-regulated anion channel blocker DCPIB on neonatal hypoxic-ischemic injury
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DOI:
10.1038/aps.2012.148
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发表时间:
2013-01-01
影响因子:
8.2
通讯作者:
Sun, Hong-shuo
Sun, Hong-shuo
中科院分区:
医学1区
文献类型:
--
作者:
Alibrahim, Ammar;Zhao, Li-yan;Sun, Hong-shuo

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目的:评价肿胀诱导的容量调节阴离子通道(VRAC)激活在新生儿缺氧缺血性损伤模型中的作用,使用选择性VRAC阻断剂4-(2-丁基-6,7-二氯-2-环戊基-茚满-1-酮-5-基)氧代丁酸(DCPIB)。在缺血发作之前,对动物ip施用DCPIB(10 mg/kg)。24小时后处死动物,切取脑冠状切片,用TTC染色和图像分析系统检查梗死面积。培养的PC 12细胞经受氧-葡萄糖剥夺(OGD)4 h。使用细胞计数试剂盒8评估细胞活力。结果:DCPIB治疗组小鼠大脑半球校正梗死体积(26.65% ± 2.23%)较对照组(45.52% ± 1.45%)显著减少(P
Aim: To evaluate the role of swelling-induced activation of volume-regulated anion channels (VRACs) in a neonatal hypoxic-ischemic injury model using the selective VRAC blocker 4-(2-butyl-6,7-dichloro-2-cyclopentyl-indan-1-on5-yl) oxobutyric acid (DCPIB).Methods: Cerebral hypoxic-ischemic injury was induced in 7-day-old mouse pups with Rice-Vannucci method: Prior to the onset of ischemia, the animals were ip administered DCPIB (10 mg/kg). The animals were sacrificed 24 h afterwards, coronal sections of the brains were cut and the areas of infarct were examined using TTC staining and an image-analysis system. Cultured PC12 cells were subjected to oxygen-glucose deprivation (OGD) for 4 h. The cellular viability was assessed using Cell Counting Kit 8. Intracellular chloride concentration [Cl-](i) was measured using 6-methoxy-N-ethylquinolinium iodide.Results: DCPIB-treated mice showed a significant reduction in hemispheric corrected infarct volume (26.65%+/- 2.23%) compared to that in vehicle-treated mice (45.52%+/- 1.45%, P