Biomechanopharmacological Study of Panax notoginseng Saponins on High Shear-induced Platelet Aggregation and Thrombosis
10.13422/j.cnki.syfjx.20241018
- VernacularTitle:三七总皂苷抑制剪切诱导血小板聚集及血栓形成的生物力药理学分析
- Author:
Yilin WANG
1
;
Jia LI
1
;
Lu LIU
1
;
Ping GONG
1
;
Jing XU
1
;
Fulong LIAO
1
;
Yun YOU
1
Author Information
1. Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences， Beijing 100700， China
- Publication Type:Journal Article
- Keywords:
arterial thrombosis;
shear stress;
platelet;
Piezo1;
von Willebrand factor （vWF）;
Panax notoginseng saponins
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(23):111-120
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the mechanisms of Panax notoginseng saponins （PNS） in inhibiting high shear-induced platelet aggregation and thrombosis via the Piezo1-mediated calcium signaling pathway. MethodBioflux1000z was used for the microfluidic assay， where platelets were stimulated with physiological shear rate （500 s-1）， pathological shear rate （12 000 s-1）， or Piezo1 agonist Yoda1 under the physiological shear rate （500 s-1）. The shear-induced platelet calcium influx and the binding of platelet with von Willebrand factor （vWF） were measured by flow cytometry. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the vWF release from platelets. The microfluidic channels were used to determine the vWF-mediated platelet aggregation and integrin αⅡbβ3 activation. A mouse model of arterial thrombosis induced by high shear stress combined with endothelial injury was established. The ultrasonic Doppler flow meter was used to monitor the cyclic flow reduction （CFR） caused by the repeated formation and shedding of thrombi， and flow cytometry was employed to examine platelet-vWF binding， on the basis of which the effect of PNS on high shear-induced arterial thrombosis was evaluated. ResultThe microfluidic assay showed that PNS decreased the high shear rate （12 000 s-1） or Yoda1-induced calcium influx， platelet-vWF binding， vWF-mediated platelet-fibrinogen binding， and vWF release from platelet alpha-granules in a dose-dependent manner. In the mouse model of high shear-induced thrombosis， PNS markedly reduced the CFR and occlusion time of the common carotid artery and inhibited platelet-vWF binding. ConclusionPNS can mitigate pathological shear-induced platelet aggregation and arterial thrombosis via influencing Piezo1/GPIbα-vWF signaling.
