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芪参益气及其成分通过抑制CD62P/PSGL-1介导的血小板-白细胞聚集体形成来减轻急性血栓栓塞性中风和颈动脉血栓形成。

QiShen YiQi and its components attenuate acute thromboembolic stroke and carotid thrombosis by inhibition of CD62P/PSGL-1-mediated platelet-leukocyte aggregate formation.

作者信息

Yu Mingxing, Xiao Guangxu, Han Linhong, Peng Li, Wang Huanyi, He Shuang, Lyu Ming, Zhu Yan

机构信息

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China.

出版信息

Biomed Pharmacother. 2023 Apr;160:114323. doi: 10.1016/j.biopha.2023.114323. Epub 2023 Feb 2.

Abstract

BACKGROUND

QiShen YiQi (QSYQ) dropping pill, a component-based Chinese medicine consisting of benefiting Qi (YQ) and activating blood (HX) components, has been reported to exert a beneficial effect on cerebral ischemia-induced stroke. However, its efficacy and pharmacological mechanism on acute thromboembolic stroke is not clear.

PURPOSE

This study is to explore the preventative effect and pharmacological mechanism of QSYQ and its YQ/HX components on the formation of platelet-leukocyte aggregation (PLA) in acute thromboembolic stroke.

STUDY DESIGN AND METHODS

In vivo thromboembolic stroke model and FeCl-induced carotid arterial occlusion models were used. Immunohistochemistry, Western blot, RT-qPCR, and flow cytometry experiments were performed to reveal the pharmacological mechanisms of QSYQ and its YQ/HX components.

RESULTS

In thromboembolic stroke rats, QSYQ significantly attenuated infarct area, improved neurological recovery, reduced PLA formation, and inhibited P-selection (CD62P)/ P-selectin glycoprotein ligand-1 (PSGL-1) expressions. The YQ component preferentially down-regulated PSGL-1 expression in leukocyte, while the HX component preferentially down-regulated CD62P expression in platelet. In carotid arterial thrombosis mice, QSYQ and its YQ/HX components inhibited thrombus formation, prolonged vessel occlusion time, reduced circulating leukocytes and P-selectin expression. PLA formation and platelet/leukocyte adhesion to endothelial cell were also inhibited by QSYQ and its YQ/HX components in vitro.

CONCLUSION

QSYQ and YQ/HX components attenuated thromboembolic stroke and carotid thrombosis by decreasing PLA formation via inhibiting CD62P/PSGL-1 expressions. This study shed a new light on the prevention of thromboembolic stroke.

摘要

背景

芪参益气滴丸是一种由益气和活血成分组成的中药复方制剂,已报道其对脑缺血性中风具有有益作用。然而,其对急性血栓栓塞性中风的疗效及药理机制尚不清楚。

目的

本研究旨在探讨芪参益气滴丸及其益气/活血成分对急性血栓栓塞性中风中血小板-白细胞聚集(PLA)形成的预防作用及药理机制。

研究设计与方法

采用体内血栓栓塞性中风模型和FeCl诱导的颈动脉闭塞模型。通过免疫组织化学、蛋白质印迹法、逆转录-定量聚合酶链反应和流式细胞术实验揭示芪参益气滴丸及其益气/活血成分的药理机制。

结果

在血栓栓塞性中风大鼠中,芪参益气滴丸显著减小梗死面积,改善神经功能恢复,减少PLA形成,并抑制P-选择素(CD62P)/P-选择素糖蛋白配体-1(PSGL-1)表达。益气成分优先下调白细胞中PSGL-1的表达,而活血成分优先下调血小板中CD62P的表达。在颈动脉血栓形成小鼠中,芪参益气滴丸及其益气/活血成分抑制血栓形成,延长血管闭塞时间,减少循环白细胞和P-选择素表达。芪参益气滴丸及其益气/活血成分在体外也抑制PLA形成以及血小板/白细胞与内皮细胞的黏附。

结论

芪参益气滴丸及其益气/活血成分通过抑制CD62P/PSGL-1表达减少PLA形成,从而减轻血栓栓塞性中风和颈动脉血栓形成。本研究为血栓栓塞性中风的预防提供了新的思路。

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