中国药理学与毒理学杂志2017,Vol.31Issue(7):707-713,7.DOI:10.3867/j.issn.1000-3002.2017.07.002
川芎嗪通过下调JNK磷酸化抑制PM2.5诱导的血管平滑肌细胞增殖
Tetramethylpyrazine inhibits PM2.5-induced vascular smooth muscle cell proliferation by down-regulating JNK phosphorylation
摘要
Abstract
OBJECTIVE To investigate the inhibitory effect and the possible mechanism of tetra-methylpyrazine (TMP) in preventing vascular smooth muscle cells (VSMCs) proliferation induced by fine particulate matter (PM2.5). METHODS PM2.520, 200 and 400 mg · L-1 was added to VSMCs for 24 h, the survival of VSMCs was measured by MTT assay, the protein levels of p-c-Jun N-terminal kinase (JNK) and fibroblast growth factor receptor-1 (FGFR-1) in the VSMCs were detected by Western blotting, while the levels of vascular cell adhesion molecule-1 (VCAM-1), endothelin-1 (ET-1) and nitric oxide (NO) in the VSMCs were analyzed by ELISA, radioimmunoassay and nitrate reductase method, respec-tively. TMP 20, 200 and 2000 mg·L-1 or a specific inhibitor of JNK SP60012510μmol·L-1 was added into the VSMCs to observe the effect of TMP. RESULTS Compared with the normal control group, PM2.5200 and 400 mg·L-1 significantly increased the A570 nm vaule, the protein levels of p-JNK and FGFR-1,the levels of VCAM-1 and ET-1, but decreased the level of NO (P<0.01), while there were no significant changes in PM2.520 mg·L-1 group. Compared with the PM2.5200 mg·L-1 group, TMP 200 and 2000 mg·L-1 pre-treatment markedly decreased the A570 nm vaule, the protein levels of p-JNK and FGFR-1, the levels of VCAM-1 and ET-1, but increased the level of NO (P<0.01), while there were no significant changes in TMP 20 mg · L-1 pre-treated group. Moreover, the effects of TMP were significantly enhanced by the co-incubation of TMP 2000 mg · L-1 with SP60012510 μmol · L-1, compared to the TMP 2000 mg · L-1 pre-treated group (P<0.05, P<0.01). CONCLUSION TMP displays a significant inhibitory effect against VSMC proliferation induced by PM2.5. The mechanism may be related to the inhibition of JNK phosphor-ylation, and the regulation of FGFR-1 protein expression and VCAM-1, ET-1 and NO levels.关键词
PM2.5/川芎嗪/c-Jun氨基端激酶/血管平滑肌细胞Key words
PM2.5/tetramethylpyrazine/JNK/vascular smooth muscle cells分类
医药卫生引用本文复制引用
万强,杨玉萍,杨雪,陈洪涛,万蝉俊,徐驲..川芎嗪通过下调JNK磷酸化抑制PM2.5诱导的血管平滑肌细胞增殖[J].中国药理学与毒理学杂志,2017,31(7):707-713,7.基金项目
国家自然科学基金(81660770) (81660770)
江西省自然科学基金(20161BAB215256) (20161BAB215256)
江西省卫生计生委科技计划(20171105)The project supported by National Natural Science Foundation of China (81660770) (20171105)
Natural Science Foundation of Jiangxi Province (2016BAB215256) (2016BAB215256)
and Science and Technology Planning Project of Health and Family Planning Commission of Jiangxi Province (20171105) (20171105)