Effect of asiaticoside on endothelial-to-mesenchymal transition in hypoxia pulmonary hypertension
10.3867/j.issn.1000-3002.2017.05.002
- VernacularTitle:积雪草苷对低氧肺动脉高压中内皮-间充质转化的作用
- Author:
Wenjing YE
;
Axiao PAN
;
Mengmeng JIN
;
Xiaochun ZHU
;
Liangxing WANG
;
Xiaobing WANG
- Keywords:
endothelial-to-mesenchymal transition;
asiaticoside;
pulmonary hypertension;
hypoxia
- From:
Chinese Journal of Pharmacology and Toxicology
2017;31(5):385-392
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effect of asiaticoside (AS) on endothelial-to-mesenchymal transition (EndoMT) in hypoxia pulmonary hypertension (HPH). METHODS Male Sprague-Dawley (SD) rats were divided into normoxia control group, hypoxia model group, and AS 25 and 50 mg · kg-1 group. Hypoxia model group and AS group were subjected to intermittent hypoxia exposure. Control group and model group received 1-1.5 mL saline daily, and AS groups were ig administrated with AS 25 and 50 mg·kg-1 for 4 weeks. Human pulmonary artery endothelial cells (HPAECs) were divided into normoxia control group and hypoxia AS groups. Hypoxia groups were cultured with AS 0, 25, 50, 100 and 200 mg·L-1 for 72 h under hypoxic (5%O2, 5%CO2) conditions. Anti-proliferation effect of AS was investigated by CCK-8 assay. Then, HPAECs were divided into normoxia control group, normoxia AS 100 mg · L-1 group, hypoxia model group, and hypoxia AS 100 mg · L-1 group. After five days of culture, migration ability of cells was detected by Transwell test. Expression of CD31 andα-SMA was detected by immunofluorescence and Western blotting in both in vivo and in vitro experiments. RESULTS In both in vivo and in vitro experiments, compared with normoxia control group, expression of CD31 was reduced (P<0.01) andα-smooth muscle actin (α-SMA) was increased (P<0.01) in hypoxia model group in both immunofluorescent analysis and Western blotting. Compared with hypoxia model group, expression of CD31 was increased andα-SMA was decreased (P<0.05, P<0.01) in AS treatment groups. Compared with normoxia control group, proliferation and migration ability of HPAEC were elevated in hypoxia model group (P<0.05). Compared with hypoxia group, AS 100 mg · L-1 depressed proliferation and migration of HPAEC under hypoxia exposure up to 72 h (P<0.05). CONCLUSION EndoMT might be involved in HPH and could be partly inhibited by AS.
