Toll-like receptor 3 activation drives the inflammatory response in oxygen-induced retinopathy in rats
Toll-like receptor 3 activation drives the inflammatory response in oxygen-induced retinopathy in rats
复制标题
Toll 样受体 3 激活可驱动大鼠氧诱导视网膜病变的炎症反应。
DOI：
10.1136/bjophthalmol-2014-305690
复制
发表时间：
2015-01-01
影响因子：
4.1
通讯作者：
Xu, Haiyan
中科院分区：
文献类型：
--
作者：
Cai, Min;Zhang, Xuedong;Xu, Haiyan
目的：缺血是导致失明的最重要原因之一。本研究的目的是探讨toll样受体3 （TLR3）在氧诱导视网膜病变（OIR）大鼠模型中影响炎症反应进展的潜在作用和机制。方法成功建立OIR大鼠模型，于出生后第17天（P17）分别接受单次玻璃体内注射聚肌苷-多胞酸（poly (I:C)）和抗tlr3抗体。病理视网膜新生血管的评估采用血红素和伊红染色和免疫组化Isolectin B4 FITC（异thyocyanate荧光素）。采用实时荧光定量PCR、免疫组织化学和western blot检测视网膜TLR3和核因子κ B （nf - κ B）表达。实时荧光定量PCR和ELISA检测白细胞介素-6 （IL-6）和肿瘤坏死因子α (TNF - α)的表达水平。结果与对照组相比，OIR大鼠视网膜中TLR3和nf - κ B基因及蛋白表达水平均显著升高。在OIR大鼠视网膜中也观察到IL-6和TNF - α表达水平升高。此外，TLR3信号通路成分，包括NF-kappa B和IL-6/TNF α，在poly（I:C）刺激下显着上调。此外，在OIR模型中预处理TLR3中和抗体可显著降低TLR3和NF-kappa B的表达，以及相关炎症因子IL-6/TNF - α的表达。结论我们的研究结果表明，TLR3信号通路的上调参与了大鼠视网膜的促炎反应。
Aims Ischaemia is one of the most important causes of blindness. The purpose of this study was to investigate the potential role and mechanisms by which toll-like receptor 3 (TLR3) influences the progression of the inflammatory response in a rat model of oxygen-induced retinopathy (OIR).Methods OIR rat models were successfully established and received single intravitreal injections of polyinosine-polycytidylic acid (poly (I:C)) and anti-TLR3 antibody, respectively, on postnatal day 17 (P17). Pathological retinal neovascularisation was evaluated by haematoxylin and eosin staining and immunohistochemistry with Isolectin B4 FITC (fluorescein isothyocyanate). Retinal expressions of TLR3 and nuclear factor kappa B (NF-kappa B) were measured using real-time PCR, immunohistochemistry and western blot. Furthermore, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF alpha) expression levels were assessed with real-time PCR and ELISA.Results Both gene and protein expression levels of TLR3 and NF-kappa B were significantly elevated in the retinas of OIR rats compared to the controls. Increased IL-6 and TNF alpha expression levels were also observed in the retinas of OIR rats. Furthermore, TLR3 signalling pathway components, including NF-kappa B and IL-6/TNF alpha, were markedly upregulated upon stimulation with poly(I:C). In addition, the pre-treatment of TLR3 neutralising antibody in OIR models significantly decreased TLR3 and NF-kappa B expressions, as well as related inflammatory factors IL-6/TNF alpha expression.Conclusions Our results suggest that upregulation of the TLR3 signalling pathway is involved in the proinflammatory response in OIR rat retinas.