羟基红花黄色素A舒张大鼠基底动脉与上调MAPK通路增强Kv通道有关  

Hydroxysafflor Yellow A Dilates Basilar Arteries of Rats by Up-Regulating MAPK Signaling Pathway and Enhancing Kv Channels

作　　者：杨蓉 赵焕新 季新燕 杨李旺 王惠洁 翟晓艳 YANG Rong;ZHAO Huanxin;JI Xinyan;YANG Liwang;WANG Huijie;ZHAI Xiaoyan(School of Basic Medicine,Shanxi University of Chinese Medicine,Jinzhong 030619)

机构地区：[1]山西中医药大学基础医学院,晋中030619

出　　处：《中药药理与临床》2023年第8期41-45,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：山西省自然科学基金面上项目(编号:202203021221199、202203021221196);山西中医药大学科技创新能力培育计划项目(编号:2020PY-JC-11)。

摘　　要：目的:探讨羟基红花黄色素A对离体大鼠基底动脉的舒张作用,并研究该作用与电压依赖性钾通道(Voltage-gated K+channels, Kv)和丝裂原活化蛋白激酶(Mitogen-activated protein kinases, MAPK)通路的关系。方法:采用离体微血管环技术研究羟基红花黄色素A对大鼠基底动脉血管环肌张力的影响,及Kv通道阻断剂4-AP、MAPK通路抑制剂SB239063和PD98059对羟基红花黄色素A舒张大鼠基底动脉血管环的影响;采用全细胞膜片钳记录方式及蛋白质印迹法(Western blot)研究羟基红花黄色素A对大鼠基底动脉平滑肌细胞Kv通道电流及Kv1.2通道蛋白表达的作用,及SB239063和PD98059对以上作用的影响。结果:羟基红花黄色素A 10、30、100μmol/L可以抑制内皮素-1(Endothelin-1,ET-1)引起的基底动脉血管环的收缩作用(P<0.01),也可浓度依赖性舒张10 nmol/L ET-1预收缩的基底动脉血管环(P<0.01);4-AP、SB239063和PD98059可以显著抑制羟基红花黄色素A对大鼠基底动脉血管环的舒张作用(P<0.01);羟基红花黄色素A可使基底动脉平滑肌细胞Kv通道电流增大、Kv1.2通道蛋白表达上调(P<0.01),SB239063和PD98059可显著抑制羟基红花黄色素A增加Kv通道电流和上调Kv1.2通道蛋白表达的作用(P<0.01)。结论:羟基红花黄色素A可舒张离体大鼠基底动脉血管环,该作用可能与上调MAPK通路和增强Kv通道有关。Objective:To investigate the dilating effect of hydroxysafflor yellow A(HSYA)on the isolated basilar arteries of rats and its relationship with voltage-gated K*channels(Kv channels)and the mitogen-activated protein kinase(MAPK)pathway.Methods:In vitro microvascular loop technique was used to study the effect of HSYA on muscular tension of basilar artery rings in rats and the effect of Kv channel blocker 4-AP and MAPK pathway inhibitors(SB239063 and PD98059)on the dilation of basilar artery rings by HSYA.The effect of HSYA on Kv channel current and Kv1.2 protein expression in rat basilar artery smooth muscle cells and the role of SB239063 and PD98059 on HSYAinduced effect were investigated with whole-cell patch clamp and Western blot,respectively.Results:HSYA(10,30,and 100μmol/L)could inhibit endothelin-1(ET-1)-induced constriction of basilar artery rings(P<0.01)and also dilate basilar artery rings preconstructed by 10 nmol/L ET-1 in a concentration-dependent manner(P<0.01).The 4-AP,SB239063,and PD98059 could markedly inhibit the dilating effect of HSYA on basilar artery rings in rats(P<0.01).HSYA could increase Kv channel current and enhance Kv1.2 protein expression in rat basilar artery smooth muscle cells(P<0.01),while SB239063 and PD98059 inhibited the HSYA-induced effects on increasing Kv channel current and enhancing Kv1.2 protein expression(P<0.01).Conclusion:HSYA can dilate isolated basilar artery rings in rats,which may be related to the up-regulation of the MAPK signaling pathway and the enhancement of Kv channels.

关 键 词：羟基红花黄色素A 大鼠基底动脉 舒张作用 丝裂原活化蛋白激酶通路 电压依赖性钾通道 

分 类 号：R285.5[医药卫生—中药学]