PD98059抑制Peroxynitrite诱导人脑血管
平滑肌细胞DDR2的表达 PD98059抑制Peroxynitrite诱导人脑血管平滑肌细胞DDR2的表达

山东大学学报(医学版) ›› 2012, Vol. 50 ›› Issue (8): 5-.

PD98059抑制Peroxynitrite诱导人脑血管
平滑肌细胞DDR2的表达 PD98059抑制Peroxynitrite诱导人脑血管平滑肌细胞DDR2的表达

万小娟1，黄凌燕1,3，张国栋2，李建峰1,2

1.山东大学附属省立医院耳鼻咽喉头颈外科，济南 250022； 2.山东省临床医学研究院
眼耳鼻喉科学研究所，济南 250022； 3.宁夏医科大学附属医院病理科，银川 750004

收稿日期:2011-12-26 出版日期:2012-08-10 发布日期:2012-08-10
通讯作者: 李建峰(1962- ),男,教授，主任医师，博士生导师，主要从事实验病理学研究。 E-mail: lijianfeng@hotmail.com
作者简介:万小娟(1978- ),女，硕士研究生，主治医师，主要从事病理学研究。
基金资助:
山东省科技厅科研基金(2006GG2202)

PD98059 inhibits Peroxynitrite-induced discoidin domain receptor2
expression in human brain vascular smooth muscle cells

WAN Xiao-juan1, HUANG Ling-yan1,3, ZHANG Guo-dong2, LI Jian-feng1,2

1. Department of Otolaryngology, Head and Neck Surgery, Provincial Hospital Affiliated to
Shandong University, Jinan 250022, China; 2. Eye, Ear, Nose and Throat Scientific Research Institute,
Shandong Institute of Clinical Medicine, Jinan 250022, China; 3. Department of Pathology,
Affiliated Hospital of Ningxia Medical College, Yinchuan 750004, China

Received:2011-12-26 Online:2012-08-10 Published:2012-08-10

摘要/Abstract

摘要：

目的探讨过氧亚硝酸盐(ONOO-)诱导人脑血管平滑肌细胞(HBVSMCs)盘状结构域受体2(DDR2)表达的机制。方法体外培养HBVSMCs，用倒置相差显微镜、吖啶橙染色法和MTT比色法对PD98059预处理的细胞进行细胞形态学及细胞生存率检测，采用Western blot及Real-time PCR技术，检测ONOO-作用下HBVSMCs中DDR2表达及施加ERK1/2抑制剂PD98059后DDR2/MMP-9表达的变化。结果 10μmol/L ONOO-诱导DDR2在蛋白及mRNA水平上呈现高表达(P<0.05)，随着ONOO-浓度的增加，DDR2逐渐呈现低表达(P<0.05)。 PD98059预处理后的HBVSMCs，无明显形态学变化，对其进行生存率检测亦无显著影响(P>0.05)。PD98059显著抑制ONOO-诱导的DDR2/MMP-9表达(P<0.05)。结论 ERK1/2信号转导途径抑制剂PD98059可以抑制ONOO-诱导的DDR2/MMP-9表达，ONOO-诱导HBVSMCs DDR2的表达机制与ERK1/2信号转导途径有关。

关键词: 过氧亚硝酸；肌，平滑，血管；盘状结构域受体2；PD98059；明胶酶B

Abstract:

Objective To explore the possible mechanism underlying peroxynitrite (ONOO-)-induced discoidin domain receptor-2(DDR2) expression in human brain vascular smooth muscle cells (HBVSMCs). Methods HBVSMCs were cultured in vitro in different concentrations of ONOO-, and PD98059, a specific inhibitor of ERK1/2. Morphology and viability of HBVSMCs pretreated with PD98059 were detected by an inverted phase contrast microscope, acridine orange staining and MTT assay. Western blot and Real-time PCR were employed to determine expressions of DDR2/ MMP-9. Results 10μmol/L of ONOO- significantly induced expression of DDR2 at both protein and mRNA levels (P<0.05). With increase in concentrations of ONOO-, expression of DDR2 was markedly decreased(P<0.05). After pretreatment on HBVSMCs with PD98059, cellular morphology and viability had no significant change by an inverted phase contrast microscope, acridine orange staining and MTT assay(P>0.05). Pretreatment on HBVSMCs with PD98059 significantly inhibited expressions of DDR2/ MMP-9 in HBVSMCs induced by 10 μmol/L of ONOO- (P<0.05). Conclusion PD98059 inhibits ONOO--induced DDR2 expression. The ERK1/2 signal transduction pathway might involve in ONOO-induced DDR2 expression in HBVSMCs.

Key words: Peroxynitrous acid; Muscle, smooth, vascular; Discoidin domain receptor 2; PD98059; Gelatinase B

中图分类号:

R363.2+1

万小娟1，黄凌燕1,3，张国栋2，李建峰1,2. PD98059抑制Peroxynitrite诱导人脑血管
平滑肌细胞DDR2的表达 PD98059抑制Peroxynitrite诱导人脑血管平滑肌细胞DDR2的表达[J]. 山东大学学报(医学版), 2012, 50(8): 5-.

WAN Xiao-juan1, HUANG Ling-yan1,3, ZHANG Guo-dong2, LI Jian-feng1,2. PD98059 inhibits Peroxynitrite-induced discoidin domain receptor2
expression in human brain vascular smooth muscle cells[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(8): 5-.

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