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三花汤通过靶向水通道蛋白4的机制对大鼠局灶性脑缺血/再灌注损伤的神经保护作用。

Neuroprotection of Sanhua Decoction against Focal Cerebral Ischemia/Reperfusion Injury in Rats through a Mechanism Targeting Aquaporin 4.

作者信息

Lu Lin, Li Hui-Qin, Li Ji-Huang, Liu Ai-Ju, Zheng Guo-Qing

机构信息

Department of Neurology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.

出版信息

Evid Based Complement Alternat Med. 2015;2015:584245. doi: 10.1155/2015/584245. Epub 2015 May 18.

Abstract

Sanhua decoction (SHD) is a famous classic Chinese herbal prescription for ischemic stroke, and aquaporin 4 (AQP4) is reported to play a key role in ischemic brain edema. This study aimed to investigate neuroprotection of SHD against focal cerebral ischemia/reperfusion (I/R) injury in rats and explore the hypothesis that AQP4 probably is the target of SHD neuroprotection against I/R rats. Lentiviral-mediated AQP4-siRNA was inducted into adult male Sprague-Dawley rats via intracerebroventricular injection. The focal cerebral ischemia/reperfusion model was established by occluding middle cerebral artery. Neurological examinations were performed according to Longa Scale. Brain water content, was determined by wet and dry weight measurement. Western blot was adopted to test the AQP4 expression in ipsilateral hippocampus. After the treatment, SHD alleviated neurological deficits, reduced brain water content and downregulated the expression of AQP4 at different time points following I/R injury. Furthermore, neurobehavioral function and brain edema after I/R were significantly attenuated via downregulation of AQP4 expression when combined with AQP4-siRNA technology. In conclusion, SHD exerted neuroprotection against focal cerebral I/R injury in rats mainly through a mechanism targeting AQP4.

摘要

三花汤(SHD)是一种治疗缺血性中风的著名经典中药方剂,据报道水通道蛋白4(AQP4)在缺血性脑水肿中起关键作用。本研究旨在探讨三花汤对大鼠局灶性脑缺血/再灌注(I/R)损伤的神经保护作用,并探讨AQP4可能是三花汤对I/R大鼠神经保护作用靶点的假说。通过脑室内注射将慢病毒介导的AQP4-siRNA导入成年雄性Sprague-Dawley大鼠体内。通过阻断大脑中动脉建立局灶性脑缺血/再灌注模型。根据Longa评分进行神经功能检查。采用干湿重法测定脑含水量。采用蛋白质免疫印迹法检测同侧海马区AQP4的表达。治疗后,三花汤在I/R损伤后的不同时间点减轻了神经功能缺损,降低了脑含水量,并下调了AQP4的表达。此外,当与AQP4-siRNA技术联合应用时,通过下调AQP4表达,I/R后的神经行为功能和脑水肿明显减轻。综上所述,三花汤对大鼠局灶性脑I/R损伤具有神经保护作用,其机制主要是通过靶向AQP4实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7ae/4452182/7b690ec076fb/ECAM2015-584245.001.jpg

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