Dioscin Reduces Vascular Damage in the Retina of db/db Mice by Inhibiting the VEGFA Signaling Pathway.

Dioscin Reduces Vascular Damage in the Retina of db/db Mice by Inhibiting the VEGFA Signaling Pathway.
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Dioscin通过抑制VEGFA信号通路来减少DB/DB小鼠视网膜的血管损伤。

DOI:
10.3389/fphar.2021.811897
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发表时间:
2021
影响因子:
5.6
通讯作者:
Yang MM
Yang MM
中科院分区:
医学2区
文献类型:
--
作者:
Wang J;Yang GY;Sun HY;Meng T;Cheng CC;Zhao HP;Luo XL;Yang MM

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糖尿病视网膜病变(DR)是糖尿病的一种并发症,严重影响患者的生活质量。VEGFA在生理状态下是维持内皮活性和血管物理性质所必需的。VEGFA在促进新生血管形成中起重要作用,因此,抑制VEGFA可以降解血管结构,减少新生血管形成。在本研究中,HERB,一个高通量的实验和参考导向的数据库,草药,用于化合物挖掘靶向VEGFA。通过分子对接筛选最可能与VEGFA相互作用的化合物。接下来,使用这些化合物来验证其是否可以在体外抑制VEGF信号通路的活性和在体内抑制新血管形成。在体外实验中,我们发现薯蓣皂苷可以抑制高糖环境下人视网膜微血管内皮细胞VEGFA-VEGFR 2信号通路的激活和细胞增殖。更重要的薯蓣皂苷干预抑制db/db小鼠视网膜中促血管生成因子的表达。结论:薯蓣皂苷可减轻db/db小鼠视网膜血管损伤,降低促血管生成因子的表达,在临床治疗DR中具有重要的应用价值。
Diabetic retinopathy (DR) is a complication of diabetes that has a serious impact on the quality of life of patients. VEGFA is necessary in the physiological state to maintain endothelial activity and physical properties of blood vessels. VEGFA plays an important role in the promotion of neovascularization; therefore, inhibition of VEGFA can degrade the structure of blood vessels and reduce neovascularization. In the present study, HERB, a high-throughput experimental and reference-oriented database of herbal medicines, was used for compound mining targeting VEGFA. The compounds most likely to interact with VEGFA were screened by molecular docking. Next, the compounds were used to verify whether it could inhibit the activity of the VEGF signaling pathway in vitro and neovascularization in vivo. In vitro, we found that dioscin could inhibit the activation of the VEGFA–VEGFR2 signaling pathway and cell proliferation of human retinal microvascular endothelial cells in a high-glucose (HG) environment. A more important dioscin intervention inhibits the expression of pro-angiogenic factors in the retinas of db/db mice. In conclusion, our study indicates that dioscin reduces the vascular damage and the expression of pro-angiogenic factors in the retina of db/db mice and implies an important and potential application of dioscin for treatment of DR in clinics.
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