PM2.5对大鼠脑基底动脉收缩功能的影响
肖雪1，王荣1，曹蕾1，沈振兴2，曹永孝1
基金项目：高等学校博士学科点专项科研基金（20100201110054） 作者简介：肖雪（1987-），女，博士生，心血管药理学 通信联系人：曹永孝（1957-），男，教授，心血管药理学.

（1. 西安交通大学医学部药理学系，西安 710061； 2. 西安交通大学环境科学与工程系，西安 710049）
摘要：目的：探讨大气细颗粒物（PM2.5）水溶性混悬液对大鼠脑基底动脉收缩的影响，并探讨机制。方法：将大鼠脑基底动脉制成1~2 mm长的环段，与PM2.5培养16h后，用血管张力描记技术记录激动剂诱导的张力。结果：脑基底动脉在0.3、1和3μg/ml PM2.5水溶混悬液中培养16 h后，其ETB和ETA受体介导的收缩反应的量效曲线明显左移，ETB受体介导收缩的Emax分别从空白组的2.27±0.03mN增加到3.52±0.05、3.99±0.04和3.28±0.05mN（n=13~14, P＜0.01）。ETA受体介导收缩的Emax分别从对照组的4.85±0.23mN增加到6.04±0.21、6.92±0.18和6.23±0.17mN（n=13~14, P＜0.01）。ERK1/2抑制剂（U0126、SB386023），能够降低PM2.5培养引起的ETB和ETA受体介导的收缩增强。p38抑制剂（SB203580），JNK抑制剂（SP600125）能降低PM2.5培养引起的ETB受体介导的收缩增15 强。结论：PM2.5培养可增强大鼠脑基底动脉ETB、ETA受体介导的收缩反应。此作用可能与ERK1/2，p38或JNK信号转导通路有关。
关键词：药理学；PM2.5；内皮素受体；脑基底动脉；大鼠
中图分类号：R122.7
 The effect of PM2.5 on contractile function of rat basilar artery
XIAO Xue1, WANG Rong1, CAO Lei1, SHEN Zhenxing2, CAO Yongxiao1
(1. Department of Pharmacology, Xi’an Jiaotong University College of Medicine, Xi’an 710061; 2. Department of Environmental Science and Engineering, Xi’an Jiaotong University, Xi’an 25 710049)
Abstract: Objective: Explore the effects of fine particulate matter (PM2.5) water-soluble suspension on contractile function of rat basilar artery and its possible mechanism. Methods: Rat basilar arteries were cut into 1~2 mm approximately, cultued with PM2.5 for 16h, and recorded the agonist-induced contractile function by myograph. Results: PM2.5 water-soluble suspension 0.3, 1, 3μg/ml culture shifted the ETB and ETA receptor-mediated contractile dose-response curve obviously to the left, and ETB receptor-mediated Emax increased from the control group of 2.27±0.03mN to the 3.52±0.05, 3.99±0.04 and 3.28±0.05mN (n=13~14, P＜0.01). The ETA receptor-mediated Emax increased from the control group of 4.85±0.23mN to 6.04±0.21, 6.92±0.18 and 6.23±0.17mN (n=11~13, P＜0.01). ERK1/2 inhibitors(U0126、SB386023)，p38 inhibitor(SB203580), JNK inhibitor(SP600125)attenuated the PM2.5-induced the ETB receptor-mediated increased contraction. ERK1/2 inhibitors(U0126、SB386023) attenuated the PM2.5-induced ETA receptor-mediated increased contraction. Conclusion: PM2.5 increased the contractile responses mediated by ETB and ETA receptors in rat basilar artery. ERK1/2, p38 or JNK intercellular signaling pathways may be involved in the functional alteration.
Key words: Pharmacology; PM2.5; Endothelin receptor; Basilar artery; Rat