摘要
目的:探讨5-羟色胺(5-HT)诱导冠状动脉收缩的机制。方法:取雄性Wistar成年大鼠,制备离体冠状动脉环,经血管张力测定仪测定动脉环的张力变化,并探讨给予不同信号通路抑制剂对5-HT诱导的冠状动脉收缩的影响。结果:首先发现给予5-HT_(2A)受体阻断剂沙格雷酯(sarpogrelate,1μmol/L)可完全消除5-HT引起的冠状动脉浓度依赖性收缩;磷脂酶C_β(PLC_β)抑制剂U73122(10μmol/L和50μmol/L)、Rho相关蛋白激酶抑制剂Y-27632(3μmol/L和10μmol/L)和蛋白激酶Cδ亚基(PKCδ)抑制剂rottlerin(3μmol/L和10μmol/L)孵育后,均可明显抑制5-HT引起的冠状动脉环收缩(P<0.05);此外,L-型钙通道(Cav1.2)阻断剂硝苯地平(1μmol/L)及细胞内钙池操纵性钙内流(SOCE)抑制剂SKF96365(10μmol/L和30μmol/L)和2-氨基乙氧基苯硼酸(2-APB,50μmol/L和100μmol/L)孵育后,5-HT诱导的血管收缩张力较未处理组明显下降(P<0.05);另外,在含硝苯地平(1μmol/L)的无钙Kerbs-Henseleit(K-H)液中,发现5-HT仍可诱导血管收缩。结论:5-HT通过激活5-HT_(2A)受体诱导冠状动脉收缩,其机制可能与PKC和Rho激酶信号通路,以及钙调控有关。
AIM： To investigate the possible mechanism of coronary artery contraction induced by 5-hydroxytryptamine（ 5-HT）. METHODS： Isolated coronary artery rings were obtained from male Wistar rats,and the vascular tension meter was used to determine the tension of the coronary artery rings. The effects of inhibitors of different signaling pathway on vascular contraction tension induced by 5-HT were observed. RESULTS： Firstly,we found that 5-HT_（2A） receptor antagonist sarpogrelate（ 1 μmol/L） completely eliminated the coronary artery contraction induced by 5-HT. Phospholipase C_β（ PLC_β） inhibitor U73122（ 10 μmol/L and 50 μmol/L）,Rho-related protein kinase inhibitor Y-27632（ 3μmol/L and 10 μmol/L） and protein kinase C δ subunit（ PKCδ） inhibitor rottlerin（ 3 μmol/L and 10 μmol/L） significantly inhibited the contraction of coronary artery ring caused by 5-HT（ P〈0. 05）. In addition,compared with the untreated group,vascular contraction tension induced by 5-HT was also decreased significantly by L-type calcium channel（ Cav1. 2） blocker nifedipine（ 1 μmol/L）,store-operated Ca^（2＋） entry（ SOCE） inhibitor SKF96365（ 10 μmol/L and 30μmol/L） and 2-aminoethoxydiphenyl borate（ 2-APB,50 μmol/L and 100 μmol/L）（ P〈0. 05）. At the same time,5-HT also induced vasoconstriction after treated with nifedipine（ 1 μmol/L） Kerbs-Henseleit（ K-H） liquid without calcium（ P〈0. 05）. CONCLUSION： 5-HT activates 5-HT_（2A） receptor induced coronary artery contraction,possibly related to the PKC/Rho kinase signaling pathway and calcium regulation.
作者
王昊
邓春玉
饶芳
邝素娟
杨慧
刘林
吴琪
徐劲松
WANG Hao;DENG Chun-yu;RAO Fang;KUANG Su-juan;YANG Hui;LIU Lin;WU Qi;xu Jing-song(Second Affiliated Hospital of Nanchang University, Nanchang 330006, China;Department of Medical Research, Guang- dong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, Guangzhou 510080, China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2018年第5期825-831,共7页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81660081
No.81470440)
江西省自然科学基金资助项目(No.20161 BAB205257)
