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심바스타틴이 인체망막색소상피세포에서 생산된 혈관내피성장인자에 미치는 효과

Effects of Simvastatin on the Expression of VEGF in Human Retinal Pigment Epithelial Cells

김나래|김경실|김경진|진희승
대한안과학회 (The Korean Ophthalmological Society)|2012.06|대한안과학회지 (Journal of The Korean Ophthalmological Society)|제53권 제6호|pp. 849-855|DOI http://dx.doi.org/10.3341/jkos.2012.53.6.849

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키워드

Oxidative stressVascular endothelial growth factorAge-related macular degenerationSimvastatinRetinal pigment epithelial cell
주제분류안과학

초록

목적: 심바스타틴(simvastatin)이 산화 스트레스하의 인체망막색소상피세포에서 생산된 혈관내피성장인자에 어떠한 영향을 미치는지알아보고자 하였다. 대상과 방법: Simvastatin과 H2O2를 농도를 달리하여 인체망막색소상피세포에 처리한 뒤 MTT assay를 통해 세포 활성도를 측정하였다. Simvastatin을 전 처치한 인체망막색소상피세포에 H2O2 100 μm을 처리하여 산화 스트레스를 준 후 ELISA를 이용하여 VEGF를측정하였다. 결과: Simvastatin 10 μm까지는 세포 활성도에 영향이 없었으나 10 μm 이상의 농도에서 세포 활성도가 감소하는 양상을 보였다. 산화스트레스 하의 인체망막색소상피세포를 5 μm 이하의 simvastatin에 전 처치 시 VEGF의 발현이 감소하였다. 노출시간에 따른 발현은3시간 노출 시 가장 감소되었으며 24시간 노출 시까지 지속되었다. 결론: Simvastatin은 산화 스트레스 하의 인체망막색소상피세포에서 VEGF의 생성을 감소시키며 VEGF의 증가가 병인으로 작용하는망막 질환을 예방하는데 도움이 될 수 있을 것으로 기대된다.

Abstract

Purpose: To examine the effect of simvastatin on vascular endothelial growth factor (VEGF) expression in cultured human retinal pigment epithelial (RPE) cells under oxidative stress. Methods: RPE cell viability was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay after 24 hours of incubation with various concentrations of simvastatin or H2O2. Cultured human RPE cells were pretreated with various concentrations of simvastatin and then incubated with 100 μm H2O2. After 24 hours of incubation, an enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the expression of VEGF. Results: Simvastatin showed no toxicity up to 10 μm, but cell viability gradually decreased with increased concentration of simvastatin. Human RPE cells showed increased VEGF expression when exposed only to H2O2. When RPE cells were preincubated with simvastatin and later exposed to H2O2, VEGF expression was relatively lower. Conclusions: Simvastatin downregulated the expression of VEGF in human RPE cells under oxidative stress. Simvastatin may have some clinical benefits in preventing retinal diseases associated with VEGF.

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