期刊
EXPERIMENTAL EYE RESEARCH
卷 86, 期 1, 页码 131-137出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exer.2007.10.003
关键词
angiogenesis; neovascularization; oxygen-induced retinopathy; rifampicin
Rifampicin, an antibacterial drug widely used in the treatment of tuberculosis and leprosy, has recently been reported to have anti-oxidative and anti-apoptotic effects. However, its anti-angiogenic effect has not been investigated. We examined its anti-angiogenic effect on tube formation and proliferation by human umbilical vein endothelial cells (HUVECs) in vitro and on retinal neovascularization in a murine oxygen-induced retinopathy model in vivo. In addition, we explored the potential mechanisms for its anti-angiogenic effect. Rifampicin significantly suppressed HUVEC tube formation and proliferation, and its effects appeared to be mediated at least in part through inhibition of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. Retinal neovasuclarization was induced in neonatal mice by returning the retina to normoxia (21% O-2) after exposure to hyperoxia (75% O-2) from postnatal day 7 (P7) to P12. Rifampicin was given subcutaneously at 20 mg/kg once a day from immediately after hyperoxia (P12) to P16. At P17, flat-mounted retinas were prepared and evaluated for pathological and physiological angiogenesis. Rifampicin significantly suppressed retinal neovascularization (versus vehicle treatment), but revascularization of the capillary-free area did not differ between vehicle and rifampicin treatment. Rifampicin has anti-angiogenic effects in vitro and in vivo, and may be useful as an anti-angiogenic agent in the treatment of retinal neovascularization diseases. (C) 2007 Elsevier Ltd. All rights reserved.
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