Qishen Yiqi Dropping Pill facilitates post-stroke recovery of motion and memory loss by modulating ICAM-1-mediated neuroinflammation
Qishen Yiqi Dropping Pill facilitates post-stroke recovery of motion and memory loss by modulating ICAM-1-mediated neuroinflammation
复制标题
芪参益气滴丸通过调节 ICAM-1 介导的神经炎症促进中风后运动和记忆丧失的恢复
DOI：
10.1016/j.biopha.2022.113325
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发表时间：
2022-06-27
影响因子：
7.5
通讯作者：
Zhu, Yan
中科院分区：
文献类型：
--
作者：
Liu, Xinyan;Xiao, Guangxu;Zhu, Yan
背景：促进患者的功能恢复是卒中管理的主要目标。然而，由于对脑卒中复杂的病理过程缺乏充分的了解，因此其治疗策略有限，因此其成就很低。芪参益气滴丸是临床上广泛应用于缺血性心血管疾病治疗的中药复方制剂。本研究通过动物实验观察了强心益气汤对急性缺血性脑卒中的保护作用，旨在探讨强心益气汤对脑卒中恢复期脑功能的影响。研究方法：采用大鼠大脑中动脉闭塞（MCAO）模型，通过神经功能缺损评分、避暗试验、步态分析、Morris水迷宫和脑组织萎缩体积等指标评价QSYQ的治疗作用。采用蛋白质组测序技术，结合免疫组化、qRT-PCR和ELISA方法，探讨QSYQ促进MCAO大鼠功能恢复的机制。通过分子对接和体外生物化学验证，对QSYQ中的活性成分进行了鉴定。结果如下：QSYQ治疗28天显着改善MCAO大鼠的神经功能，步态，自发活动，空间记忆，并减少脑萎缩。缺血脑区蛋白质组学分析及后续生物信息学研究表明，益气养阴汤干预可明显调节脑卒中后神经炎症反应，其中ICAM-1起主导作用。特别是，QSYQ逆转了MCAO大鼠脑ICAM-1的高表达，并降低了脑组织和血清中TNF-α、IL-6和IL-1 β的含量。在体外，通过免疫荧光染色发现芪参芪中的活性成分迷迭香酸可明显抑制氧糖剥夺/复氧损伤引起的ICAM-1的表达。结论：QSYQ通过下调ICAM-1介导的神经炎症反应，有效促进脑卒中后大鼠运动障碍和记忆力的恢复，迷迭香酸是其主要活性成分之一。
Background: Promotion of functional recovery in patients is the primary goal of stroke management. However, its achievement is low due to the lack of full understanding of the complex pathological process of stroke and therefore limited therapeutic strategies. Qishen Yiqi Dropping Pill (QSYQ) is a component-based Chinese med-icine that has been widely used in clinical treatment of ischemic cardiovascular diseases. Our previous studies indicated that QSYQ were protective for acute ischemic stroke in animal models and this study aimed to investigate the effect of QSYQ on brain function during stroke recovery. Methods: The therapeutic effects of QSYQ were evaluated by neurological deficit score, dark avoidance test, gait analysis, Morris water maze and brain tissue atrophy volume in a rat model of middle cerebral artery occlusion (MCAO) with ischemia for 60 min. The underlying mechanisms of QSYQ accelerating the functional recovery of MCAO rats was then revealed using proteomic sequencing and validated by immunohistochemistry, qRT-PCR and ELISA assays. The active components in QSYQ were elucidated by molecular docking and verified bio-chemically in vitro. Results: QSYQ treatment for 28 days significantly improved the neurological function, gait, spontaneous activity, spatial memory, and reduced brain atrophy in MCAO rats. Proteomic analysis of ischemic brain region and the following bioinformatics studies showed that QSYQ intervention markedly modulated neuroinflammatory re-sponses post stroke, in which ICAM-1 played a dominant role. In particular, QSYQ reversed high cerebral expression of ICAM-1 in MCAO rats and decreased the content of TNF-alpha, IL-6 and IL1 beta in brain tissue and serum. In vitro, it was found that the active component rosmarinic acid in QSYQ evidently inhibit the expression of ICAM-1 caused by oxygen glucose deprivation/reoxygenation injury via using immunofluorescence staining. Conclusion: QSYQ effectively accelerates the recovery of motor impairment and memory loss in rats after stroke via downregulation of ICAM-1-mediated neuroinflammation, and rosmarinic acid is one of its main active components.