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依达拉奉通过抑制水通道蛋白-4减轻脑缺血损伤。

Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4.

机构信息

Division of Laboratory and Vascular Medicine, Field of Cardiovascular and Respiratory Disorders, Department of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.

出版信息

Biochem Biophys Res Commun. 2009 Dec 25;390(4):1121-5. doi: 10.1016/j.bbrc.2009.09.015. Epub 2009 Sep 6.

Abstract

Aquaporin-4 (AQP4) plays a role in the generation of post-ischemic edema. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the central nervous system (CNS) associated with altered brain water balance. Edaravone, a free radical scavenger, is used for the treatment of acute ischemic stroke (AIS) in Japan. In this study, edaravone significantly reduced the infarct area and improved the neurological deficit scores at 24h after reperfusion in a rat transient focal ischemia model. Furthermore, edaravone markedly reduced AQP4 immunoreactivity and protein levels in the cerebral infarct area. In light of observations that edaravone specifically inhibited AQP4 in a rat transient focal ischemia model, we propose that edaravone might reduce cerebral edema through the inhibition of AQP4 expression following cerebral infarction.

摘要

水通道蛋白 4(AQP4)在缺血后水肿的产生中起作用。因此,AQP4 功能的药物调节可能为中风、肿瘤相关水肿、癫痫、创伤性脑损伤和其他与脑水平衡改变相关的中枢神经系统(CNS)疾病的治疗提供一种新的治疗策略。依达拉奉是一种自由基清除剂,在日本用于治疗急性缺血性中风(AIS)。在这项研究中,依达拉奉在大鼠短暂性局灶性缺血模型再灌注后 24 小时显著减少了梗死面积并改善了神经功能缺损评分。此外,依达拉奉明显降低了脑梗死区域的 AQP4 免疫反应性和蛋白水平。鉴于依达拉奉在大鼠短暂性局灶性缺血模型中特异性抑制 AQP4 的观察结果,我们提出依达拉奉可能通过抑制脑梗死后脑组织中 AQP4 的表达来减轻脑水肿。

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