Inhibitory effect of Samul-tang on retinal neovascularization in oxygen-induced retinopathy.
Inhibitory effect of Samul-tang on retinal neovascularization in oxygen-induced retinopathy.
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DOI：
10.1186/s12906-015-0800-7
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发表时间：
2015-08-12
影响因子：
--
通讯作者：
Kim J
中科院分区：
文献类型：
--
作者：
Lee YM;Kim CS;Jo K;Sohn EJ;Kim JS;Kim J
视网膜新生血管是增殖性糖尿病视网膜病变、早产儿视网膜病变和年龄相关性黄斑变性中视力丧失的常见原因。三木汤（SMT）是东亚地区广泛使用的一种传统草药，日文又称下素汤，中文又称四物汤。本研究旨在评价SMT对氧致视网膜病变（OIR）小鼠视网膜致病性血管生成的抑制作用。小鼠从出生后第7天（P7-P12）开始，连续5天暴露于75%浓度的氧气中。然后将小鼠暴露于室内空气中，每天腹腔注射一次SMT (10 mg/kg或50 mg/kg)，连续5天（P12-P16）。在P17上，我们测量了视网膜新生血管，并评估了血管生成相关蛋白的表达和mRNA中基因表达水平的变化。SMT减少了OIR小鼠中央视网膜的面积并减少了视网膜新生血管的形成。蛋白质阵列显示SMT降低了SDF-1蛋白的表达水平。实时荧光定量PCR结果显示，与正常对照小鼠相比，OIR小鼠视网膜中HIF-1α、SDF-1、CXCR4和VEGF mRNA水平升高。然而，SMT降低了OIR小鼠HIF-1α、SDF-1、CXCR4和VEGF mRNA的水平。我们首次阐明SMT抑制OIR小鼠缺血性视网膜病变诱导的视网膜致病性血管生成。SMT通过下调HIF-1α、SDF-1、CXCR4和VEGF显著抑制视网膜新生血管形成。根据我们的研究结果，SMT可能是一种有效的治疗缺血性视网膜病变的草药。
Retinal neovascularization is a common cause of vision loss in proliferative diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration. Samul-tang (SMT) is a widely used traditional herbal medicine in East Asia and is also known as Shimotsu-to in Japanese and Si-Wu decoction in Chinese. This study was designed to evaluate the inhibitory effect of SMT on retinal pathogenic angiogenesis in a mouse model of oxygen-induced retinopathy (OIR). The mice were exposed to a 75 % concentration of oxygen for five days, starting on postnatal day 7 (P7-P12). The mice were then exposed to room air and were intraperitoneally injected with SMT (10 mg/kg or 50 mg/kg) once per day for five days (P12-P16). On P17, we measured retinal neovascularization and evaluated both the expression of angiogenesis-related proteins and changes in the gene expression level in the mRNA. SMT reduced the area of the central retina and reduced retinal neovascularization in OIR mice. The protein array revealed that SMT reduced the level of SDF-1 protein expression. Quantitative real-time PCR revealed that the HIF-1α, SDF-1, CXCR4 and VEGF mRNA levels in the retinas of OIR mice were elevated compared with those of normal control mice. However, SMT decreased the levels of HIF-1α, SDF-1, CXCR4 and VEGF mRNA in OIR mice. We are the first to elucidate that SMT inhibits the retinal pathogenic angiogenesis induced by ischemic retinopathy in OIR mice. SMT significantly inhibited retinal neovascularization by downregulating HIF-1α, SDF-1, CXCR4 and VEGF. Based on the results of our study, SMT could be a useful herbal medicine for treating ischemic retinopathy.