期刊
ACTA PHARMACOLOGICA SINICA
卷 31, 期 10, 页码 1395-1400出版社
ACTA PHARMACOLOGICA SINICA
DOI: 10.1038/aps.2010.167
关键词
hyperhomocysteinemia; danshensu; endothelin; nitric oxide; tumor necrosis factor-alpha; intercellular adhesion molecule-1
资金
- National Basic Research Program of China [2005CB523301]
- National Natural Science Foundation of China [30801503, 30772810, 30873325]
- Chinese Ministry of Education
Aim: To examine whether danshensu could protect vascular endothelia in a rat model of hyperhomocysteinemia. Methods: The model was established by feeding rats with a methionine-rich diet (1 g.kg(-1)d(-1)) for 3 months. Immediately following the discontinuation of methionine-rich diet, rats were treated with danshensu (67.5 mg.kg(-1)d(-1), po) or saline for 3 additional months. One group of rats receiving vitamin mixture (folic acid, vitamin B12 and vitamin B6) was included as a positive control. One group of rats not exposed to methionine-rich diet was also included as a blank control. The expression of tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) protein in the descending aorta was examined using immunohistochemistry and Western blot. Homocysteine and blood concentration of endothelin and nitric oxide (NO) was also examined. Results: Methionine-rich diet resulted in accumulation of foam cells, up-regulated expression of TNF-alpha and ICAM-1 in the descending aorta, and significantly increased serum homocysteine. Plasma endothelin concentration was significantly increased; NO was decreased. Danshensu treatment, either simultaneous to methionine-rich diet or afterwards, attenuated the above mentioned changes. Conclusion: Chronic treatment with danshensu could prevent/attenuate the formation of atherosclerosis. Potential mechanisms include inhibited expression of representative proinflammatory cytokines and adhesion molecules in arterial endothelia. Changes in homocysteine and circulating molecules that control vascular contraction/relaxation via endothelial cells (eg, endothelin and NO) were also implicated.
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