Effect of the blockade of the IL-23-Th17-IL-17A pathway on streptozotocin-induced diabetic retinopathy in rats.
Effect of the blockade of the IL-23-Th17-IL-17A pathway on streptozotocin-induced diabetic retinopathy in rats.
复制标题
阻断 IL-23-Th17-IL-17A 通路对链脲佐菌素诱导的大鼠糖尿病视网膜病变的影响。
DOI：
10.1007/s00417-014-2842-9
复制
发表时间：
--
影响因子：
2.7
通讯作者：
Zhang X
中科院分区：
文献类型：
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作者：
Xu H;Cai M;Zhang X
目的辅助性T细胞17（Th 17）在链脲佐菌素（STZ）诱导的视网膜病变的慢性炎症和免疫反应中起重要作用。本研究旨在探讨IL-23-Th 17-IL-17 A通路通过血视网膜屏障对STZ诱导的糖尿病大鼠视网膜病变的影响。方法采用流式细胞术检测STZ治疗组和野生型大鼠外周血单个核细胞中IL-17 A + CD 4 +T细胞的比例。使用实时PCR测量视网膜中的IL-17 A mRNA水平。采用ELISA试剂盒检测外周血和视网膜中IL-17 A的蛋白表达。使用苏木精和伊红（H&E）染色检查野生型和STZ处理的大鼠中的视网膜结构。此外，使用埃文斯蓝技术定量血视网膜屏障的渗透性。结果与野生型组相比，STZ治疗的大鼠外周血单核细胞中IL-17 A + CD 4 +T细胞的比例显着增加。IL-17 A蛋白水平在外周血和视网膜也显着升高STZ治疗的大鼠。然而，当将抗IL 23 Rp 19抗体注射到STZ处理的大鼠眼中的玻璃体腔中一周时，视网膜色素上皮细胞变得明显紧密，微血管和内皮细胞显著减少。IL-17 A mRNA和蛋白在视网膜中的表达也显着下降，与安慰剂治疗group.ConclusionsThis研究提供了进一步了解IL-23-Th 17-IL-17 A途径在STZ诱导的糖尿病大鼠视网膜病变的功能。局部注射抗IL-23 Rp 19抗体可改善血-视网膜屏障的结构，从而提供使用玻璃体内抗IL-23 Rp 19抗体进行治疗的可能性。
PurposeT helper 17 (Th17) cells are believed to play a critical role in the chronic inflammatory and immune response in streptozotocin (STZ)-induced retinopathy. The purpose of our study was to investigate the effect of the IL-23–Th17–IL-17A pathway via the blood–retinal barrier on STZ-induced diabetic retinopathy in rats.MethodsThe ratio of IL-17A+CD4+T cells in peripheral blood mononuclear cells of STZ-treated and wild-type rats was determined using flow cytometry. The IL-17A mRNA levels in the retinas were measured using real-time PCR. The protein expression of IL-17A in the peripheral blood and retinas was measured using an ELISA kit. The retinal structure in the wild-type and STZ-treated rats was examined using hematoxylin and eosin (H&E) staining. Additionally, the permeability of the blood–retinal barrier was quantified using the Evans blue technique.ResultsThe ratio of IL-17A+CD4+T cells in peripheral blood mononuclear cells was markedly increased in rats treated with STZ compared to the wild-type group. IL-17A protein levels in the peripheral blood and retinas were also significantly elevated in STZ-treated rats. However, when the anti-IL 23Rp19 antibody was injected into the vitreous cavity in the eyes of STZ-treated rats for a period of one week, retinal pigment epithelium cells became markedly tighter, and micrangium and endothelial cells were significantly reduced. The expression of IL-17A mRNA and protein in the retina also decreased significantly compared with the placebo-treated group.ConclusionsThis study provided further insight into the function of the IL-23–Th17–IL-17A pathway in STZ-induced diabetic retinopathy in rats. Local injection of the anti-IL-23Rp19 antibody may improve the structure of the blood–retinal barrier, thus offering the potential for treatment using intravitreal anti-IL-23Rp19 antibodies.