Anti-inflammatory properties of shikonin contribute to improved early-stage diabetic retinopathy.
Anti-inflammatory properties of shikonin contribute to improved early-stage diabetic retinopathy.
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DOI：
10.1038/srep44985
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发表时间：
2017-03-21
影响因子：
4.6
通讯作者：
Cheng YW
中科院分区：
文献类型：
--
作者：
Liao PL;Lin CH;Li CH;Tsai CH;Ho JD;Chiou GC;Kang JJ;Cheng YW
糖尿病视网膜病变（DR）是糖尿病的一种主要微血管并发症，可导致视网膜血管渗漏、神经元功能障碍和视网膜内细胞凋亡。在这项研究中，我们将STZ与全身缺氧（10%O2）相结合，以更快地诱导C57 BL/6小鼠的早期视网膜病变。我们还通过使用视网膜色素上皮（RPE）细胞比较了高糖条件与缺氧（1%O2）相结合与低糖条件的影响，RPE细胞是外血视网膜屏障的重要组成部分，其损伤与视网膜病变有关。在DM/缺氧C57 BL/6小鼠的视网膜中，使用视网膜电图（ERG）、眼底照相（FP）、眼底荧光素血管造影（FFA）和光学相干断层扫描（OCT）发现异常a波和b波活动、黄白色斑点、荧光增强和视网膜厚度减少。紫草素剂量依赖性地（0.5-50 mg/kg，口服）预防DM/缺氧引起的损伤。在眼组织中，紫草素的给药也减弱了DM/缺氧诱导的凋亡前蛋白BAX的表达以及炎性蛋白环氧合酶-2（考克斯-2）和诱导型一氧化氮合酶（iNOS）的产生。我们还表明，紫草素管理救援高糖/缺氧（1%O2）诱导的炎症，减少连接蛋白的表达，和渗透性的RPE细胞。这些结果表明，紫草素治疗可以防止与DR相关的视力丧失。
Diabetic retinopathy (DR), a major microvascular complication of diabetes, leads to retinal vascular leakage, neuronal dysfunction, and apoptosis within the retina. In this study, we combined STZ with whole-body hypoxia (10% O2) for quicker induction of early-stage retinopathy in C57BL/6 mice. We also compared the effects of a high glucose condition combined with hypoxia (1% O2) to a low glucose condition by using retinal pigment epithelial (RPE) cells, which are a crucial component of the outer blood-retinal barrier and the damage is related to retinopathy. In the retina of DM/hypoxic C57BL/6 mice, abnormal a-wave and b-wave activity, yellowish-white spots, hyperfluorescence, and reduced retinal thickness were found using electroretinography (ERG), fundus photography (FP), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT). Shikonin dose-dependently (0.5–50 mg/kg, per os) prevented DM/hypoxia-induced lesions. In eye tissue, administration of shikonin also attenuated DM/hypoxia-induced pre-apoptotic protein BAX expression as well as the production of inflammatory proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). We also demonstrated that shikonin administration rescues high glucose/hypoxia (1% O2)-induced inflammation, decreased junction protein expression, and permeability in RPE cells. These results indicate that shikonin treatment may prevent the loss of vision associated with DR.