中国临床药理学杂志2018，Vol.34Issue(9)：1100-1104,5.DOI:10.13699/j.cnki.1001-6821.2018.09.026
芹菜素对舒张大鼠基底动脉的作用及机制研究
Effect of apigenin on the vasodilatory of basilar artery in rats and it mechanism
摘要
Abstract
Objective To study the spasmolytic effect and the underlying mechanism of apigenin in isolated rat basilar artery.Methods Healthy male rats were euthanized by exsanguination.The rat brain was removed and transferred immediately into physiological salt solution.The rat basilar arteries were isolated and cut into 2 mm-long rings under the microscope.Diastolic test:the different segments of the same blood vessel were randomly divided into two groups:the control group (solvent dimethylsulfoxide,diastolic) and the experimental group (apigenin 1-100 μmol · L-1,diastolic).Inhibition of contraction test:the same blood vessel was divided into the control group,low,medium and high dose experimental groups based on the dosage of administration (apigenin 0,10,30,100 μmol · L-1 respectively).The duration of administration was at least 10 min.Calcium ion (Ca2+) deprivation and specific inhibitors:an inhibitor of protein kinase C (Go6983),an inhibitor of extracellular signal-regulated kinase (PD98059),an inhibitor of Rho-associated kinase (Y-27632),an inhibitor of p38 Mitogen-activated protein kinase (SB239063) were used to explore the possible involvement of modulation of Ca2 + availability and activities of protein kinases in apigenin-induced vasorelaxation.The vascular myogenic tone was recorded with a wire myograph.Half maximal diastolic concentration (RC50),half maximal inhibitory concentration (IC50),maximal diastolic rate and maximal inhibition rate were calculated.Results After the administration,apigenin 1 ～ 100 μmol · L-1 concentration-dependently relaxed the arterial rings precontracted with either KCl 60 mmol · L-1,U46619 0.3 μmol · L-1 or vasopressin (VP,3 μmol · L-1) and the RC50 values were (24.27 ±1.14),(4.1 ±1.16),(1.9±1.33) μmol · L-1 respectively.Comparison between experimental groups with control group,the difference had significantly (all P ＜ 0.01).Incubation with apigenin 10 ～ 100 μmol · L-1 shifted the concentration-contraction curves of KCl,U46619,VP or Ca2+ to the right with the maximal contractions depressed.The IC50values of low,medium and high dose experimental groups against KCl,U46619,VP or Ca2+ were (77.73 ± 1.72),(14.91 ± 1.31),(20.66 ± 1.21),(7.53 ± 1.02) μmol · L-1 respectively.Comparison between three doses experimental groups with control group,the difference had significantly (all P ＜ 0.01).Both intracellular Ca2+ release dependent and extracellular Ca2+ influx dependent contractions were reduced after preincubation with apigenin by (24.53 ± 5.32) ％ and (48.58 ± 8.92) ％.Preincubation with Go6983 and PD98059,but not Y-27632 and SB239063 attenuated apigenin-induced vasorelaxation.Relaxation rate of Go6983 made API on the KCl,U46619 shrinkingwere decreased (40.33 ± 2.51)％,(36.51±5.13)％;Relaxation rate of PD98059 made API on the KCl,U46619 shrinkingwere decreased (25.84 ± 3.86)％,(21.80 ± 5.95)％.Compared with control group (without apigenin or inhibitors intervention),the difference were statistically significant (P ＜0.05,P ＜0.01).Conclusion Apigenin are spasmolytic against a variety of vasoconstrictors in rat basilar artery.Reduction of Ca2 + availability,modulation of activities of extracellular signal-regulated kinase and protein kinase C may be,at least in part,contributory to vasorelaxant effects of apigenin.关键词
芹菜素/基底动脉/血管舒张/蛋白激酶Key words
apigenin/basilar artery/vasodilatation/protein kinase分类
医药卫生引用本文复制引用
郭鹏美,刘宇,景宜馨,宋奇颖,董苗苗,董丽娜,张明升..芹菜素对舒张大鼠基底动脉的作用及机制研究[J].中国临床药理学杂志,2018,34(9):1100-1104,5.基金项目
国家自然科学基金资助项目(81603111 （）
81773738) （）
山西省“1331工程”重点学科建设计划基金资助项目[晋教科(2017)6号] （2017）
