ERK1/2和p38MAPK在介导CGRP和AngⅡ诱导血管平滑肌细胞Nox1表达中的作用  

Role of ERK1/2 and p38MAPK in the expression of Nox1 in A10 vascular smooth muscle cell induced by Ang Ⅱ and CGRP

作　　者：张晓一[1] 于潇华[2] 刘玉环[2] 杨丽[2] 王珍[2] 阳芳[2] 秦旭平[2] 曾泗宇[3] 

机构地区：[1]长治医学院药学系药理教研室 [2]南华大学药物药理研究所血管生物学实验室 [3]广东省第二人民医院药物临床试验基地

出　　处：《中国临床药理学与治疗学》2017年第1期13-19,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金(30572192;81173060);广东省自然科学基金(2015A030310076)

摘　　要：目的:探讨胞外信号调节激酶1/2(ERK1/2)和p38丝裂原激活蛋白激酶(p38MAPK)在降钙素基因相关肽(CGRP)和血管紧张素Ⅱ(Ang Ⅱ)诱导血管平滑肌细胞NADPH氧化酶-1(Nox1)表达中的作用。方法:体外培养鼠源性A10血管平滑肌细胞株(A10VSMC),用Ang Ⅱ或/和CGRP作为处理因素,MTT法检测细胞增殖活力;流式细胞术检测细胞周期分布;Western blot检测ERK1/2和p38MAPK总蛋白和磷酸化蛋白以及Nox1蛋白的表达水平。结果:与对照组和CGRP组相比,Ang Ⅱ在诱导A10VSMC活力和增殖的同时,亦能增加磷酸化ERK1/2和p38MAPK信号激酶和Nox1的表达。CGRP预孵育细胞30 min却能显著抑制Ang Ⅱ诱导的细胞增殖活力、Nox1蛋白、磷酸化ERK1/2和p38MAPK的表达;二苯基碘(DPI)能抑制Ang Ⅱ诱导的细胞增殖、磷酸化p38MAPK及Nox1表达,但不能抑制Ang Ⅱ诱导的ERK1/2磷酸化。p38MAPK阻断剂SB203580不但能抵消Ang Ⅱ诱导的Nox1表达作用,而且能协同CGRP抑制Ang Ⅱ诱导的Nox1表达。而ERK1/2阻断剂PD98059对CGRP和/或Ang Ⅱ诱导Nox1表达作用的影响无统计学意义。结论:Ang Ⅱ诱导A10VSMC增殖与激活Nox1有关,CGRP抑制Ang Ⅱ诱导的Nox1表达,可能主要通过抑制p38MAPK信号途径发挥作用,而与ERK1/2信号途径无显著关系。AIM ：To explore the role of extracel- lular signal-regulated kinasel/2 （ ERK1/2 ） and p38-Mitogen-activated protein kinase （p38MAPK） in expression of nicotinic amide adenine dinucleotide phosphate （NADPH） oxidase-1 （ Noxl ） in vascular smooth muscle cell （VSMC） induced by Angiotensin II （Ang II ） and calcitonin gene-related peptide （ CGRP ）. METHODS ： Mouse-derived A10VSMC was cultured in vitro, the cell viability and the dis- tribution of cell cycle was detected by MTY and flow cytometry, respectively; Western blot was used to determine the protein levels of ERK1/2, p38MAPK and Noxl. RESULTS： Compared with control or CGRP groups, the A10VSMC proliferation, protein levels of p-ERK1/2 and p-p38MAPK and Noxl were elevated in the Ang II group, which were decreased by pretreatment of CGRP for 30 min. DPI （ Noxl inhibitor） also inhibited the A10VSMC proliferation, protein levels of p-p38MAPK and Noxl but not p- ERK1/2 induced by Ang II. SB203580 （p38MAPK inhibitor） but not PD98059 （ERK1/2 inhibitor） en- hanced the inhibitory effect CGRP on the cell prolif- eration and Noxl expression induced by Ang II. CONCLUSION： The A10VSMC proliferation induced by Ang II is related to increase of Noxl ex- pression, and the inhibitory effect of CGRP on Noxl expression induced by Ang II in the A10VSMC pro- liferation phases maybe mainly associated with p38MAPK activity but not the ERK1/2 activity.

关 键 词：血管紧张素Ⅱ 降钙素基因相关肽 血管平滑肌细胞 NADPH氧化酶 丝裂原激活蛋白激酶 

分 类 号：R965.2[医药卫生—药理学]