Jiang Youde, Thakran Shalini, Bheemreddy Rajini, Coppess William, Walker Robert J, Steinle Jena J
Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States of America; VA Medical Center, Memphis, Tennessee, United States of America.
Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
PLoS One. 2015 Apr 14;10(4):e0125505. doi: 10.1371/journal.pone.0125505. eCollection 2015.
Sodium salicylate has been reported to reduce markers of diabetic retinopathy in a type 1 rat model. Because rates of type 2 diabetes are on the rise, we wanted to determine whether salicylate could improve insulin resistance in a type 2 rat model, as well as improve retinal function. We treated lean and obese BBZDR/Wor type 2 diabetic rats with salicylate in their chow for 2 months. Prior to salicylate treatment, rats underwent an electroretinogram to measure retinal function. After 2 months of treatment, rats underwent an additional electroretinogram prior to sacrifice. In addition to the animal model, we also treated retinal endothelial cells (REC) and rat Müller cells with salicylate and performed the same analyses as done for the rat retinal lysates. To investigate the role of salicylate in insulin signaling, we measured TNFα and caspase 3 levels by ELISA, as well as performed Western blotting for insulin receptor substrate 1, insulin receptor, SOCS3, and pro- and anti-apoptotic markers. Data demonstrated that salicylate significantly improved retinal function, as well as reduced TNFα and SOCS3-induced insulin resistance in all samples. Overall, results suggest that salicylate is effective in reducing insulin resistance in the retina of type 2 diabetic rat models.
据报道,在1型大鼠模型中,水杨酸钠可降低糖尿病视网膜病变的标志物。由于2型糖尿病的发病率正在上升,我们想确定水杨酸盐是否能改善2型大鼠模型中的胰岛素抵抗以及改善视网膜功能。我们用含有水杨酸盐的食物喂养瘦型和肥胖型BBZDR/Wor 2型糖尿病大鼠2个月。在水杨酸盐治疗前,大鼠接受视网膜电图检查以测量视网膜功能。治疗2个月后,大鼠在处死前再次接受视网膜电图检查。除了动物模型外,我们还用水杨酸盐处理视网膜内皮细胞(REC)和大鼠穆勒细胞,并对大鼠视网膜裂解物进行相同的分析。为了研究水杨酸盐在胰岛素信号传导中的作用,我们通过酶联免疫吸附测定法测量肿瘤坏死因子α(TNFα)和半胱天冬酶3水平,并对胰岛素受体底物1、胰岛素受体、细胞因子信号转导抑制因子3(SOCS3)以及促凋亡和抗凋亡标志物进行蛋白质印迹分析。数据表明,水杨酸盐显著改善了视网膜功能,并降低了所有样本中TNFα和SOCS3诱导的胰岛素抵抗。总体而言,结果表明水杨酸盐在降低2型糖尿病大鼠模型视网膜中的胰岛素抵抗方面是有效的。