辅酶Q_(10)经蛋白激酶A/胞浆型磷脂酶A_(2)信号通路抑制血小板血栓素A_(2)的生成  

Coenzyme Q_(10) Attenuates Platelet Thromboxane A_(2) Generation through Regulating the Protein Kinase A/Cytosolic Phospholipase A2 Signaling Pathway

作　　者：牙甫礼 张春梅 陈彬林 谷仕艳 贾小娥 YA Fuli;ZHANG Chunmei;CHEN Binlin;GU Shiyan;JIA Xiao'e(Institute of Preventive Medicine,School of Public Health,Dali University,Dali 671000,China;Hekou Customs of the People's Republic of China,Hekou 661300,China;Department of Nutrition,Maternity and Child Health Care of Guangxi Zhuang Autonomous Region,Nanning 530000,China)

机构地区：[1]大理大学公共卫生学院,预防医学研究所,云南大理671000 [2]河口海关,云南河口661300 [3]广西壮族自治区妇幼保健院营养科,广西南宁530000

出　　处：《食品科学》2021年第9期130-136,共7页Food Science

基　　金：大理大学2020年度高层次人才科研启动基金项目(KY2096107240);大理大学2018年度博士科研启动基金项目(KYBS2018006)。

摘　　要：目的:血小板来源血栓素A_(2)(thromboxane A_(2),TxA_(2))可诱发动脉粥样硬化和血栓形成,辅酶Q_(10)(coenzyme Q_(10),CoQ_(10))可以抑制血小板活化、聚集和血栓形成。本实验旨在通过体外实验探讨CoQ_(10)对血小板TxA_(2)生成的影响及其调控机制。方法:用不同浓度(0、1、10、100μmol/L)CoQ_(10)与健康人纯化血小板在体外共同孵育50 min,在激动剂激活条件下,采用酶联免疫吸附测定法测定血小板分泌TxB_2水平;用Western blot蛋白免疫印迹法检测胞浆型磷脂酶A_(2)(cytosolic phospholipase A_(2),cPLA_(2))蛋白的磷酸化水平。结果:CoQ_(10)显著抑制多种激动剂(如凝血酶、胶原和Convulxin)诱导的血小板TxA_(2)生成;Western blot结果显示CoQ_(10)下调凝血酶和胶原诱导的血小板cPLA_(2)磷酸化水平;cPLA_(2)特异性抑制剂苯乙酮与CoQ_(10)联合使用时,对血小板TxA_(2)的生成没有协同效果;此外,蛋白激酶A(protein kinase A,PKA)特异性抑制剂H89可完全逆转CoQ_(10)对激动剂诱导的血小板cPLA_(2)磷酸化和TxA_(2)生成的抑制作用。结论:CoQ_(10)具有显著抑制激动剂诱导的血小板TxA_(2)生成的作用,其机制主要是调控PKA/c PLA_(2)介导的信号通路。Objective:Thromboxane A_(2)(TxA_(2))derived from platelets can facilitate atherosclerosis and thrombosis.Previous studies have demonstrated that coenzyme Q10(CoQ_(10))attenuates platelet activation,aggregation and thrombus formation.Our present study aimed to investigate the effect of CoQ_(10)on TxA_(2)generation and to clarify the underlying mechanisms.Methods:Gel-filtered platelets prepared from heathy adults were incubated with different concentrations of CoQ_(10)(0,1,10 and 100μmol/L)for 50 min.After agonist activation,the level of TxB2 secreted from platelets was determined by enzymelinked immunosorbent assay.The phosphorylation of cytosolic phospholipase A_(2)(cPLA_(2))was measured by Western blot.Results:CoQ_(10)significantly inhibited platelet TxA_(2)generation induced by several agonists,including thrombin,collagen and convulxin.Western blot showed that CoQ_(10)significantly down-regulated thrombin-and collagen-induced cPLA_(2)phosphorylation.Moreover,pyrrophenone,a cPLA_(2)specific inhibitor,showed no any additive effects on TxA_(2)generation when combined with CoQ_(10).Furthermore,the inhibitory effect of CoQ_(10)on agonist-induced platelet cPLA_(2)phosphorylation and TxA_(2)generation was almost completely reversed by protein kinase A(PKA)inhibitor H89.Conclusion:CoQ_(10)can attenuate agonist-induced platelet TxA_(2)generation,and the mechanism is mainly through regulating the PKA/cPLA_(2)signaling pathway.

关 键 词：辅酶Q_(10) 血小板 血栓素A_(2) 胞浆型磷脂酶A_(2) 心血管疾病 

分 类 号：R151.4[医药卫生—营养与食品卫生学]