
浏览全部资源
扫码关注微信
402160 重庆,重庆医科大学附属永川医院中心实验室
[李远,E-mail: liyuan_1985999@163.comLI Yuan, E-mail: liyuan_1985999@163.com
收稿:2022-12-29,
修回:2023-07-06,
纸质出版:2023-10-15
移动端阅览
黄小静, 张天聪, 高雪梅, 等. 三七三醇皂苷主要成分抑制剪切力诱导的血小板活化和聚集[J]. 陆军军医大学学报, 2023,45(19):2037-2044.
Xiaojing HUANG, Tiancong ZHANG, Xuemei GAO, et al. Main components of
黄小静, 张天聪, 高雪梅, 等. 三七三醇皂苷主要成分抑制剪切力诱导的血小板活化和聚集[J]. 陆军军医大学学报, 2023,45(19):2037-2044. DOI: 10.16016/j.2097-0927.202212175.
Xiaojing HUANG, Tiancong ZHANG, Xuemei GAO, et al. Main components of
目的
2
研究三七三醇皂苷主要成分对剪切力诱导的血小板活化和聚集的影响。
方法
2
建立狭窄微流控芯片模型,采用微流控芯片技术评价在不同浓度(0.05、0.1、0.25、0.5 mg/mL)及不同剪切率(1 500、4 500、9 000 s
-1
)条件下Rg1、Re和R1对剪切力诱导的血小板聚集影响;采用流式细胞术定量分析Rg1、Re和R1对高剪切力诱导的血小板活化(P-选择素和PAC-1)的影响;采用PL-12分析仪检测Rg1、Re和R1对AA和ADP诱导的血小板聚集的影响。
结果
2
Rg1、Re和R1呈浓度依赖性抑制高剪切力诱导的血小板聚集(
P
<
0.01),而对较低剪切力无抑制作用,其中Re抑制作用最强,三者的IC
50
分别为0.1、0.07、0.2 mg/mL,当3种化合物在相同浓度下联合使用时没有观察到协同作用。Rg1、Re和R1抑制P-选择素和PAC-1的表达(
P
<
0.01),抑制效果与聚集实验结果一致。Rg1、Re和R1能够抑制AA和ADP诱导的血小板聚集(
P
<
0.05)。
结论
2
三七三醇皂苷主要成分通过抑制剪切力诱导的血小板聚集发挥新的抗血小板活性。
Objective
2
To determine the effects of main components (Rg1
Re and R1) of
Panax notoginseng
saponins on platelet activation and aggregation induced by shear stress.
Methods
2
A narrow microfluidic chip model was established
and used to evaluate the effects of
Rg1
Re and R1 at different concentrations (0.05
0.1
0.25 and 0.5 mg/mL) on shear-induced platelet aggregation under different shear rates (1 500
4 500 and 9 000 s
-1
). Flow cytometry was used to quantitatively detect the shear-induced platelet activation (P-selectin and PAC-1) after the treatment of Rg1
Re and R1. PL-12 analyzer was performed to measure the effects of Rg1
Re and R1 on platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP).
Results
2
Rg1
Re and R1 inhibited platelet aggregation induced by high shear stress in a concentration-dependent manner (
P
<
0.01)
but had no such inhibitory effect under lower shear stress. Among the 3 components
Re had the strongest inhibitory effect
and their IC
50
value was 0.1
0.07
and 0.2 mg/mL
respectively. No synergistic effect was observed when the 3 components were used together at the same dose. Rg1
Re and R1 inhibited the expression of P-selectin and PAC-1 (
P
<
0.01)
which was consistent with the results of the aggregation experiment. In addition
the 3 components also could inhibit platelet aggregation induced by AA and ADP.
Conclusion
2
The main components of
Panax notoginseng
saponins exert their antiplatelet activity by inhibiting shear-induced platelet aggregation.
YE T, SHI H X, PHAN-THIEN N, et al . The key events of thrombus formation: platelet adhesion and aggregation[J ] . Biomech Model Mechanobiol, 2020, 19(3): 943-955. DOI: 10.1007/s10237-019-01262-x.
KOENEN R R, BINDER C J. Platelets and coagulation factors: established and novel roles in atherosclerosis and atherothrombosis[J]. Atherosclerosis, 2020, 307: 78-79. DOI: 10.1016/j.atherosclerosis.2020.07.008.
XIONG Y Y, BATH P M. Antiplatelet therapy for transient ischemic attack and minor stroke[J]. Stroke, 2020, 51(11): 3472-3474. DOI: 10.1161/STROKEAHA.120.031763.
KAMRAN H, JNEID H, KAYANI W T, et al . Oral antiplatelet therapy after acute coronary syndrome: a review[J ] . JAMA, 2021, 325(15): 1545-1555. DOI: 10.1001/jama.2021.0716.
SHIOZAKI S, TAKAGI S, GOTO S. Prediction of molecular interaction between platelet glycoprotein ibα and von Willebrand factor using molecular dynamics simulations[J]. J Atheroscler Thromb, 2016, 23(4): 455-464. DOI: 10.5551/jat.32458.
PUSHIN D M, SALIKHOVA T Y, ZLOBINA K E, et al . Platelet activation via dynamic conformational changes of von Willebrand factor under shear[J ] . PLoS One, 2020, 15(6): e0234501. DOI: 10.1371/journal.pone.0234501..
NESBITT W S, WESTEIN E, TOVAR-LOPEZ F J, et al . A shear gradient-dependent platelet aggregation mechanism drives thrombus formation[J ] . Nat Med, 2009, 15(6): 665-673. DOI: 10.1038/nm.1955.
JAIN A, GRAVELINE A, WATERHOUSE A, et al . A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function[J ] . Nat Commun, 2016, 7: 10176. DOI: 10.1038/ncom ms10176.
SHATTIL S J, NEWMAN P J. Integrins: dynamic scaffolds for adhesion and signaling in platelets[J]. Blood, 2004, 104(6): 1606-1615. DOI: 10.1182/blood-2004-04-1257.
GONG H X, SHEN B, FLEVARIS P, et al . G protein subunit Galpha13 binds to integrin alphaIIbbeta3 and mediates integrin "outside-in" signaling[J ] . Science, 2010, 327(5963): 340-343. DOI: 10.1126/science.1174779.
RANA A, WESTEIN E, NIEGO B, et al . Shear-dependent platelet aggregation: mechanisms and therapeutic opportunities[J ] . Front Cardiovasc Med, 2019, 6: 141. DOI: 10.3389/fcvm.2019.00141.
GAO Y, GAO C Y, ZHU P, et al . Ginsenoside Re inhibits vascular neointimal hyperplasia in balloon-injured carotid arteries through activating the eNOS/NO/cGMP pathway in rats[J ] . Biomedecine Pharmacother, 2018, 106: 1091-1097. DOI: 10.1016/j.biopha.2018.07.044.
ZHOU Q, JIANG L, XU C H, et al . Ginsenoside Rg1 inhibits platelet activation and arterial thrombosis[J ] . Thromb Res, 2014, 133(1): 57-65. DOI: 10.1016/j.thromres.2013.10.032.
QI H Y, HUANG Y L, YANG Y, et al . Anti-platelet activity of panaxatriol saponins is mediated by suppression of intracellular calcium mobilization and ERK2/p38 activation[J ] . BMC Complement Altern Med, 2016, 16: 174. DOI: 10.1186/s12906-016-1160-7.
闫海峰, 代向东, 樊克涛, 等. 人参皂苷Re对ADP、PAF、AA诱导家兔血小板聚集功能的影响[J]. 天津中医药大学学报, 2016, 35(5): 310-313.
YAN H F, DAI X D, FAN K T, et al . Effection of ginsenoside Re on ADP, PAF, AA-induced platelet aggregation[J ] . J Tianjin Univ Tradit Chin Med, 2016, 35(5): 310-313.
ZHANG T C, LIU L, HUANG X J, et al . Application of microfluidic chip technology to study the inhibitory effect of tetramethylpyrazine on platelet aggregation, activation, and phosphatidylserine exposure mediated by pathological high shear rate[J ] . Blood Coagul Fibrinolysis, 2023, 34(1): 47-60. DOI: 10.1097/MBC.0000000000001179.
张天聪, 陈丹, 廖娟, 等. 生理性流动条件下血小板在玻璃表面的聚集行为[J]. 医用生物力学, 2022, 37(3): 425-432.
ZHANG T C, CHEN D, LIAO J, et al . Platelet aggregation on glass surface under physiological flow condition[J ] . J Med Biomech, 2022, 37(3): 425-432.
XU Z Y, XU Y, XIE X F, et al . Anti-platelet aggregation of Panax notoginseng triol saponins by regulating GP1BA for ischemic stroke therapy[J ] . Chin Med, 2021, 16(1): 12. DOI: 10.1186/s13020-021-00424-3..
VARGA-SZABO D, PLEINES I, NIESWANDT B. Cell adhesion mechanisms in platelets[J]. Arterioscler Thromb Vasc Biol, 2008, 28(3): 403-412. DOI: 10.1161/ATVBAHA.107.150474.
FEGHHI S, MUNDAY A D, TOOLEY W W, et al . Glycoprotein ib-Ⅸ-Ⅴ complex transmits cytoskeletal forces that enhance platelet adhesion[J ] . Biophys J, 2016, 111(3): 601-608. DOI: 10.1016/j.bpj.2016.06.023.
YIN H, STOJANOVIC A, HAY N, et al . The role of Akt in the signaling pathway of the glycoprotein Ib-Ⅸ induced platelet activation[J ] . Blood, 2008, 111(2): 658-665. DOI: 10.1182/blood-2007-04-085514.
CHEN Z S, LI T L, KAREEM K, et al . The role of PI3K/Akt signaling pathway in non-physiological shear stress-induced platelet activation[J ] . Artif Organs, 2019, 43(9): 897-908. DOI: 10.1111/aor.13465.
LEON C, ALEX M, KLOCKE A, et al . Platelet ADP receptors contribute to the initiation of intravascular coagulation[J ] . Blood, 2004, 103(2): 594-600. DOI: 10.1182/blood-2003-05-1385.
RIVERA J, LOZANO M L, NAVARRO-NÚÑEZ L, e t al . Platelet receptors and signaling in the dynamics of thrombus formation[J ] . Haematologica, 2009, 94(5): 700-711. DOI: 10.3324/haematol.2008.003178.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621