Endothelin Receptor-A (ETa) Inhibition Fails to Improve Neonatal Hypoxic-Ischemic Brain Injury in Rats
Endothelin Receptor-A (ETa) Inhibition Fails to Improve Neonatal Hypoxic-Ischemic Brain Injury in Rats
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DOI：
10.1007/978-3-7091-0693-8_35
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发表时间：
2011-01-01
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影响因子：
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通讯作者：
Zhang, John H.
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文献类型：
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作者：
Khatibi, Nikan H.;Lee, Lillian K.;Zhang, John H.
脑缺氧缺血是新生儿死亡和残疾的重要原因。它是大脑缺氧和葡萄糖循环不足的结果，引发长期的脑损伤和细胞死亡。越来越多的证据表明，内皮素受体- a （ETA）的激活在介导脑损伤中起重要作用。在这项研究中，我们研究了ABT-627在新生儿HI损伤大鼠中抑制ETA受体的作用。出生第10天的Sprague-Dawley鼠仔（n=91）分为假手术组（n=28）、HI组（载药组，n=32）和ABT-627剂量为3 mg/kg的HI组（n=31）。Rice-Vannucci模型通过结扎右侧颈总动脉诱导缺血，随后在37℃的室内以8%的氧气进行2小时的缺氧。术后评估分别在损伤后48小时和4周进行。在急性时间点，研究指标包括脑水肿、梗死体积和体重变化。损伤后4周进行神经行为测试。我们的研究结果表明ABT-627对测量参数没有影响。本研究表明，治疗后使用ABT-627阻断ETA受体并不能改善新生儿HI损伤大鼠的神经预后。
Cerebral hypoxia-ischemia (HI) is an important cause of mortality and disability in newborns. It is a result of insufficient oxygen and glucose circulation to the brain, initiating long-term cerebral damage and cell death. Emerging evidence suggests that endothelin receptor-A (ETA) activation can play an important role in mediating brain damage. In this study, we investigated the role of ETA receptor inhibition using ABT-627 in neonatal HI injured rats. Postnatal day 10 Sprague-Dawley rat pups (n=91) were assigned to the following groups: sham (n=28), HI (vehicle, n=32), and HI with ABT-627 at 3 mg/kg (n=31). The Rice-Vannucci model was used to induce ischemia by ligating the right common carotid artery, followed by a 2 h hypoxic episode using 8% oxygen in a 37 degrees C chamber. Postoperative assessment was conducted at 48 h after injury and again at 4 weeks. At the acute time point, investigative markers included cerebral edema, infarction volume, and body weight change. Neurobehavioral testing was measured at 4 weeks post-injury. Our findings indicated that ABT-627 had no effect on the measured parameters. This study suggests that ETA receptor blockade using ABT-627 post-treatment fails to improve neurological outcomes in neonatal HI injured rats.