Tetramethylpyrazine inhibits PM2.5-induced vascular smooth muscle cell proliferation by down-regulating JNK phosphorylation
10.3867/j.issn.1000-3002.2017.07.002
- VernacularTitle: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
- Author:
Qiang WAN
1
;
ping Yu YANG
;
Xue YANG
;
tao Hong CHEN
;
jun Chan WAN
;
Ri XU
Author Information
1. 江西中医药大学附属医院心血管病科
- Keywords:
PM2.5;
tetramethylpyrazine;
JNK;
vascular smooth muscle cells
- From:
Chinese Journal of Pharmacology and Toxicology
2017;31(7):707-713
- CountryChina
- Language:Chinese
-
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.
