Alterations of tau and Camk2 in acute stroke and effects of a multicomponent drug

Yue Wu, Rui Zhou, Menglan Wang, Jing Xu, Yi Zhang, Junying Wei, Hongjun Yang
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Abstract

Abstract Background Stroke is one of the leading causes of death around the world. The sequelae of ischemic stroke cause drastic effects on the quality of life for patients. Sanwujiaowan (SWJW) is a mixture prepared with 5 herbal medicines (Aconiti Lateralis Radix Praeparata, Aconiti Kusnezoffii Radix, Polygoni Multiflori Radix, Aconiti Radix, and Olibanum), with a long history of application in treating the sequelae of stroke. Objectives To provide evidence and decipher the mechanism of SWJW in alleviating stroke. Materials and Methods In this article, we expanded the indicators of SWJW by an integrated strategy based on signature metabolomics, target proteins, and bioinformatics and probed into the mechanism of SWJW intervention in ischemic stroke in a rat model. Results The results indicated that SWJW protected rats from nerve damage during the acute phase of ischemic stroke by regulating tau phosphorylation via the PI3K/Akt pathway. Conclusions This study, for the first time, proved that the reduction of phosphorylated tau was harmful for the neural function in the acute phase of ischemic stroke. Meanwhile, the pathological changes of phosphorylated tau proteins were detected in stroke and recalled by SWJW. This finding may provide a new reference for formulating treatment strategies for the acute phase of ischemic stroke.
急性脑卒中中 tau 和 Camk2 的变化以及一种多成分药物的作用
摘要 背景 脑卒中是全球死亡的主要原因之一。缺血性中风的后遗症会严重影响患者的生活质量。三拗丸(SWJW)是由五味中药(附子、乌药、何首乌、附子、乌药)配制而成的混合物,在治疗中风后遗症方面有着悠久的应用历史。目的 为西南黄芪缓解中风提供证据并破译其作用机制。材料与方法 本文通过基于特征代谢组学、靶蛋白和生物信息学的综合策略,扩展了西南黄芪的指标,并在大鼠模型中探究了西南黄芪干预缺血性中风的机制。结果 结果表明,SWJW 通过 PI3K/Akt 通路调节 tau 磷酸化,保护大鼠在缺血性中风急性期免受神经损伤。结论 本研究首次证实,磷酸化 tau 的减少对缺血性脑卒中急性期的神经功能有害。同时,在脑卒中中检测到了磷酸化 tau 蛋白的病理变化,并通过 SWJW 进行了召回。这一发现可为缺血性脑卒中急性期治疗策略的制定提供新的参考。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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