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

作　　者：郭鹏美 刘宇[1] 景宜馨[1] 宋奇颖 董苗苗 董丽娜[1] 张明升[1] GUO Peng - mei, LIU Yu, JING Yi - xin, SONG Qi - ying, DONG Miao - miao, DONG Li - na, ZHANG Ming - sheng(Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, Chin)

机构地区：[1]山西医科大学药理教研室,太原030001

出　　处：《中国临床药理学杂志》2018年第9期1100-1104,共5页The Chinese Journal of Clinical Pharmacology

基　　金：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]

摘　　要：目的研究芹菜素(API)对大鼠离体基底动脉的血管张力的影响及其作用机制。方法雄性大鼠断头处死后,立刻取出脑组织放在0.9%Na Cl溶液中,在显微镜下分离出基底动脉,剪成长约2 mm的血管环备用。舒张实验:将同一根血管的不同段随机分为2组,对照组(溶剂二甲基亚砜,舒张)和实验组(API1~100μmol·L^(-1),舒张)。抑制收缩实验:用自身前后对照,将同一段血管从前到后依次分为对照组和低、中、高3个剂量(API 0,10,30,100μmol·L^(-1))实验组,给药时间均至少10 min。钙去除和抑制剂:蛋白激酶C抑制剂(Go6983)、细胞外信号调节激酶抑制剂(PD98059)、Rho相关酶抑制剂(Y-27632)及p38丝裂原活化蛋白激酶抑制剂(SB239063),用于观察API的血管作用与细胞内外钙和激酶的关系。以微血管张力测定仪测肌张力值,计算半舒张浓度(RC_(50))、最大舒张率、半抑制浓度(IC_(50))和最大抑制率。结果给药后,实验组对氯化钾(KCl)、血栓素类似物A_2(U46619)或加压素(VP)预收缩的血管环的RC_(50)值分别为(24.27±1.14),(4.1±1.16),(1.9±1.33)μmol·L^(-1),与对照组(0)相比,差异均有统计学意义(均P<0.01)。低、中、高3个剂量实验组的IC_(50)值分别为(77.73±1.72),(14.91±1.31),(20.66±1.21),(7.53±1.02)μmol·L^(-1),与对照组(0)相比,差异均有统计学意义(均P<0.01)。API 30μmol·L^(-1)对细胞内钙和细胞外钙介导收缩的抑制率分别为(24.53±5.32)%和(48.58±8.92)%,Go6983使API对KCl、U46619收缩的舒张率分别减少(40.33±2.51)%和(36.51±5.13)%,PD98059使API对KCl、U46619收缩的舒张率分别减少(25.84±3.86)%和(21.80±5.95)%,与无API或抑制剂干预的对照组相比,差异均有统计学意义(P<0.05,P<0.01)。结论API对大鼠基底动脉具有明显的舒张作用,其机制可能与降低钙利用、改变细胞外信号调节激酶、蛋白激酶C活性有关。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（ apigenin0,10,30,100 μmol· L^-1 respectively）. The duration of administration was at least 10 min. Calcium ion（ Ca^（2＋））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 Ca^2＋availability and activities of protein kinases in apigenin-induced vasorelaxation. The vascular myogenic tone was recorded with a wire myograph. Half maximal diastolic concentration（ RC（50））,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. 3μmol·L^-1 or vasopressin（ VP,3 μmol·L^-1） and the RC（50） 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 10100

关 键 词：芹菜素 基底动脉 血管舒张 蛋白激酶 

分 类 号：R972.4[医药卫生—药品]