血小板胆固醇、脂筏与功能间的关系探究
作者:
作者单位:

(1.苏州大学苏州医学院病理与病理生理学系,江苏省苏州市 215123;2.苏州大学苏州医学院免疫学系,江苏省苏州市 215123;3.苏州大学唐仲英血液学研究中心,江苏省苏州市 215123)

作者简介:

郑家宝,硕士,研究方向为胆固醇稳态与动脉粥样硬化,E-mail:jiabaozheng01@163.com。

基金项目:

国家自然科学基金项目(81470564、81970371);江苏高校优势学科建设工程资助项目


Investigation of the relationships among cholesterol, lipid raft and platelet function
Author:
Affiliation:

1.Department of Pathology and Pathophysiology, Suzhou, Jiangsu 215123, China;2.Department of Immunology, Soochow Medical School, Soochow University, Suzhou, Jiangsu 215123, China;3.Cyrus Tang Medical Institute, Soochow University, Suzhou, Jiangsu 215123, China)

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    摘要:

    目的]探究胆固醇对血小板脂筏含量和血小板功能的调控作用。 [方法]利用体外孵育甲基β环糊精(MβCD)和体内提升外周血总胆固醇水平来移除和负载血小板胆固醇。霍乱毒素B染色联合流式细胞术检测血小板脂筏含量;荧光抗体染色结合流式细胞术检测P选择素和活化型整合素αⅡbβ3的表达水平;Annexin V标记结合流式细胞术检测磷脂外翻水平;体外实验体系及鼠尾出血实验检测血小板的聚集能力。 [结果]B淋巴细胞上脂筏的含量随着胆固醇的移除而降低,体外孵育MβCD移除血小板胆固醇反而显著提高其脂筏水平(P<0.05)。与此一致,体内胆固醇负载增加B淋巴细胞上的脂筏含量却降低血小板的脂筏含量(P<0.05)。移除胆固醇后增加的脂筏并不利于血小板的活化与聚集功能。体内胆固醇的负载下调血小板脂筏含量(P<0.05),增强其应答低浓度刺激剂的活化聚集与凝血能力,此增强作用在移除胆固醇后消失。 [结论]血小板胆固醇是调控血小板脂筏含量和血小板功能的关键调节因子,可负向调节脂筏,促进血小板活化并增强其凝血功能。

    Abstract:

    Aim To investigate the role of cholesterol in the regulation of lipid raft and the function of platelets. Methods Using in vitro incubation of methyl β-cyclodextrin (MβCD) and in vivo elevation of peripheral blood total cholesterol levels to remove and load platelet cholesterol, respectively. Cholera toxin B staining combined with flow cytometry was used to detect platelet lipid raft content, fluorescence antibody staining combined with flow cytometry was used to detect the expression levels of P-selectin and activated integrin αⅡbβ3, annexin V labeling combined with flow cytometry was used to detect the level of phospholipid efflux, in vitro experimental system and rat tail bleeding experiment were used to detect platelet aggregation ability. Results The content of lipid raft on B lymphocytes decreased with the removal of cholesterol, while in vitro incubation of MβCD to remove platelet cholesterol significantly increased its lipid raft level (P<0.05). Consistent with this, in vivo cholesterol loading increased the lipid raft content of B lymphocytes but decreased the lipid raft content of platelets (P<0.05). The increase in lipid raft after removing cholesterol was not conducive to platelet activation and aggregation function. In vivo cholesterol loading downregulated platelet lipid raft content (P<0.05), enhanced its ability to respond to low concentration stimulant for activation aggregation and coagulation, and this enhancing effect disappeared after cholesterol removal. Conclusion Platelet cholesterol is a key regulator of platelet lipid raft content and platelet function, which can negatively regulate lipid raft, promote platelet activation, and enhance their coagulation function.

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郑家宝,周璇,何兆芬,王安妮,唐朝君,赵颖.血小板胆固醇、脂筏与功能间的关系探究[J].中国动脉硬化杂志,2024,32(10):835~842.

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  • 收稿日期:2023-11-01
  • 最后修改日期:2024-06-26
  • 在线发布日期: 2024-10-22