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四君子汤对氧诱导性视网膜病变视网膜新生血管形成的抑制作用。

Inhibitory effect of Samul-tang on retinal neovascularization in oxygen-induced retinopathy.

作者信息

Lee Yun Mi, Kim Chan-Sik, Jo Kyuhyung, Sohn Eun Jin, Kim Jin Sook, Kim Junghyun

机构信息

Korean Medicine-Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon, 305-811, South Korea.

出版信息

BMC Complement Altern Med. 2015 Aug 12;15:271. doi: 10.1186/s12906-015-0800-7.

DOI:10.1186/s12906-015-0800-7
PMID:26264147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4534021/
Abstract

BACKGROUND

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).

METHOD

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

视网膜新生血管形成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。参术汤(SMT)是一种在东亚广泛使用的传统草药,在日语中也被称为四物汤,在中文中被称为四物汤。本研究旨在评估参术汤对氧诱导性视网膜病变(OIR)小鼠模型中视网膜病理性血管生成的抑制作用。

方法

从出生后第7天(P7 - P12)开始,将小鼠置于75%浓度的氧气环境中5天。然后将小鼠置于室温空气中,并每天腹腔注射一次参术汤(10 mg/kg或50 mg/kg),持续5天(P12 - P16)。在P17时,我们测量了视网膜新生血管形成,并评估了血管生成相关蛋白的表达以及mRNA中基因表达水平的变化。

结果

参术汤减少了OIR小鼠中央视网膜的面积并减少了视网膜新生血管形成。蛋白质阵列显示参术汤降低了SDF - 1蛋白表达水平。定量实时PCR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,参术汤降低了OIR小鼠中HIF - 1α、SDF - 1、CXCR4和VEGF mRNA的水平。

结论

我们首次阐明参术汤抑制OIR小鼠缺血性视网膜病变诱导的视网膜病理性血管生成。参术汤通过下调HIF - 1α、SDF - 1、CXCR4和VEGF显著抑制视网膜新生血管形成。基于我们的研究结果,参术汤可能是一种治疗缺血性视网膜病变的有用草药。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb5f/4534021/e9f934d1df24/12906_2015_800_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb5f/4534021/8999821de720/12906_2015_800_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb5f/4534021/714ca124a7e6/12906_2015_800_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb5f/4534021/ae2bd76526dc/12906_2015_800_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb5f/4534021/e9f934d1df24/12906_2015_800_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb5f/4534021/8999821de720/12906_2015_800_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb5f/4534021/714ca124a7e6/12906_2015_800_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb5f/4534021/ae2bd76526dc/12906_2015_800_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb5f/4534021/e9f934d1df24/12906_2015_800_Fig4_HTML.jpg

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