Liu Xinyan, Xiao Guangxu, Wang Yule, Shang Ting, Li Zhixiong, Wang Huanyi, Pu Lihua, He Shuang, Shao Rui, Orgah John Owoicho, Zhu Yan
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biomedicine, 220 Dongting Road, TEDA, Tianjin 300457, China.
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biomedicine, 220 Dongting Road, TEDA, Tianjin 300457, China; Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, XiHu District, Hangzhou 310058, China.
Biomed Pharmacother. 2022 Sep;153:113325. doi: 10.1016/j.biopha.2022.113325. Epub 2022 Jun 27.
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 medicine 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.
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 biochemically in vitro.
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 responses 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-α, IL-6 and IL1β 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.
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.
促进患者功能恢复是中风治疗的首要目标。然而，由于对中风复杂病理过程缺乏全面了解，治疗策略有限，这一目标的达成率较低。芪参益气滴丸（QSYQ）是一种中药复方制剂，已广泛应用于缺血性心血管疾病的临床治疗。我们之前的研究表明，芪参益气滴丸对动物急性缺血性中风具有保护作用，本研究旨在探讨芪参益气滴丸对中风恢复过程中脑功能的影响。
通过神经功能缺损评分、暗回避试验、步态分析、莫里斯水迷宫试验以及大脑中动脉闭塞（MCAO）缺血60分钟大鼠模型的脑组织萎缩体积，评估芪参益气滴丸的治疗效果。然后，利用蛋白质组测序揭示芪参益气滴丸加速MCAO大鼠功能恢复的潜在机制，并通过免疫组织化学、qRT-PCR和ELISA试验进行验证。通过分子对接阐明芪参益气滴丸中的活性成分，并在体外进行生化验证。
芪参益气滴丸治疗28天可显著改善MCAO大鼠的神经功能、步态、自发活动、空间记忆，并减少脑萎缩。对缺血脑区的蛋白质组分析及后续生物信息学研究表明，芪参益气滴丸干预可显著调节中风后的神经炎症反应，其中细胞间黏附分子-1（ICAM-1）起主要作用。特别是，芪参益气滴丸可逆转MCAO大鼠大脑中ICAM-1的高表达，并降低脑组织和血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL1β）的含量。在体外，通过免疫荧光染色发现，芪参益气滴丸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表达。
芪参益气滴丸通过下调ICAM-1介导的神经炎症，有效促进中风后大鼠运动功能障碍和记忆丧失的恢复，迷迭香酸是其主要活性成分之一。
