软坚清脉颗粒改善下肢动脉硬化闭塞症中氯吡格雷抵抗作用与机制探讨

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中文摘要：目的:探索软坚清脉颗粒抗血小板及改善氯吡格雷抵抗(CR)的确切机制.方法:临床观察下肢动脉硬化闭塞症(ASO)患者接受软坚清脉颗粒治疗前后的血小板反应单位和血清P-选择素水平的变化,并检测治疗前后血小板中P2Y12 mRNA和蛋白含量差异.随后探索软坚清脉颗粒对ASO小鼠巨核细胞中IκB/IKK/NF-κB信号通路中关键蛋白和mRNA的影响,观察鼠血小板上P2Y12蛋白表达,并检测血小板功能与活性.结果:软坚清脉颗粒能够改善ASO患者的CR,并协同氯吡格雷发挥抗血小板作用,其可能机制与调控血小板上P2Y12受体表达有关.动物实验发现软坚清脉颗粒能够促进ASO小鼠巨核细胞中IκB的磷酸化,抑制IKK和p65的磷酸化,抑制IKK蛋白表达,降低P2Y12 mRNA转录和P2Y12受体蛋白表达.结论:软坚清脉颗粒能够通过抑制IκB/IKK/NF-κB信号通路降低血小板上ADP受体P2Y12的表达,协同氯吡格雷发挥抗血小板作用来改善ASO患者的CR.

外文标题：Effects and mechanism of Ruanjian Qingmai Granules on improving clopidogrel resistance in arteriosclerosis obliterans patients

外文摘要：Objective:The study explored the exact mechanism of Ruanjian Qingmai Granules(RJQM)'s antiplatelet activity,followed by an investigation into its potential to ameliorate Clopidogrel resistance(CR).Methods:Platelet reactivity units and serum P-selectin levels were clinically observed in arteriosclerosis obliterans(ASO)patients before and after RJQM treatment,while differences in P2Y12 mRNA and P2Y12 protein levels in platelets were detected before and after the treatment.Subsequently,we investigated the impact of RJQM on essential proteins and mRNAs in the IκB/IKK/NF-κB signaling pathway in megakaryocytes of ASO mice.We also examined P2Y12 protein expression in mice platelets and monitored platelet function and activity.Results:Our findings indicate that RJQM improved CR and acted synergistically with clopidogrel to produce antiplatelet effects in ASO patients.Additionally,our observations suggest that RJQM may regulate P2Y12 receptor expression on platelets,providing a possible mechanism for its antiplatelet effects.Animal experiments demonstrated that RJQM promoted IκB phosphorylation while inhibiting IKK and p65 phosphorylation and expression of IKK protein.Additionally,it reduced P2Y12 mRNA transcription and the expression of P2Y12 receptor protein in megakaryocytes of ASO mice.Conclusion:RJQM improved cognitive rehabilitation in ASO patients by inhibiting the IκB/IKK/NF-κB signaling pathway,thereby reducing the expression of ADP receptor P2Y12 on platelets and working synergistically with clopidogrel to exert antiplatelet effects.

外文关键词：

Ruanjian Qingmai GranulesArteriosclerosis obliteransClopidogrel resistanceAntiplateletPlatelet function

作者：

张永康、宗媛、殷康力、王御震、曹烨民

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作者单位：

上海中医药大学附属上海市中西医结合医院脉管病诊疗中心,上海 200086

关键词：

软坚清脉颗粒下肢动脉硬化闭塞症氯吡格雷抵抗抗血小板血小板功能

基金：

国家自然科学基金"重大新药创制"科技重大专项上海市科委科技创新行动计划虹口区"国医强优"三年行动计划(第二轮)(2022-2024)杨浦区科委与卫生健康委科研项目

项目编号：

821743822019ZX09201004-002-09120Z21900200HKGYQYXM-2022-07YPQ202108

出版年：

2024

中华中医药杂志

中华中医药学会

中华中医药杂志

CSTPCD北大核心

影响因子：1.135

ISSN：1673-1727

年,卷(期)：2024.39(5)