标题：Danshensu protects vascular endothelia in a rat model of hyperhomocysteinemia
作者：Yang, Rui-xue; Huang, Shan-ying; Yan, Fang-fang; Lu, Xiao-ting; Xing, Yi-fan; Liu, Yan; Liu, Yun-fang; Zhao, Yu-xia
作者机构：[Liu, Yun-fang] Shandong Univ, Sch Med, Dept Diag, Jinan 250012, Peoples R China.; [Yang, Rui-xue; Huang, Shan-ying; Yan, Fang-fang; Lu, Xiao-ting; 更多
通讯作者地址：[Liu, YF]Shandong Univ, Sch Med, Dept Diag, Jinan 250012, Peoples R China.
来源：ACTA PHARMACOLOGICA SINICA
关键词：hyperhomocysteinemia; danshensu; endothelin; nitric oxide; tumor; necrosis factor-alpha; intercellular adhesion molecule-1
摘要：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.