眼科新进展2017，Vol.37Issue(10)：926-930,5.DOI:10.13389/j.cnki.rao.2017.0235
沉默信息调节因子相关酶1(SIRT1)调控p38MARK信号通路对糖尿病视网膜病变大鼠视网膜神经节细胞的保护作用及机制
Protective effects and mechanism of SIRT1 for the regulation of p38 MAPK pathway on retinal ganglion cells in rats with diabetic retinopathy
摘要
Abstract
Objective To investigate the effect of silment information regulator factor related enzymes 1 (SIRT1) on the apoptosis of retinal ganglion cells (RGCs) in rats with diabetic retinopathy and its downstream molecular mechanisms.Methods Together 60 healthy male Sprague-Dawley rats were collected and randomly divided into normal group,diabetic group,SIRTI activator-resveratrol treatment group (treatment group),and diabetic rat model was induced by intraperitoneal injection of streptozotocin at 60 mg · kg-1 in the latter two group rats,while the normal group was injected with sodium citrate buffer at 60 mg · kg-1.Then,after 72 h,rats with blood glucose ＞ 16.7 mmol · L-1 were designated as diabetic rats by blood glucose test.Then each rat in the treatment group was treated with SIRT1 activator-resveratrol at 20 g · kg-1 once a day at the 2nd day after the success of the model,and the normal group and diabetic group were given methylene chloride.Finally,after immunohistochemical staining for retina,TUNEL assay was used to evaluate the apoptosis of RGCs,while the expression of SIRTI,p38 MAPK and Caspase-3 protein was detected by Western blot.Results The apoptotic index of RGCs in the normal group,diabetic group and treatment group was (0.848+0.131)％,(19.038 + 1.327)％,(10.461 + 1.089)％ respectively at 8 weeks,and the difference among the three groups was statistically significant (F =670.497,P =0.000),while the differences between each two groups were also statistically significant (all P =0.000).Furthermore,when compared with the normal group (0.132 ± 0.043),the expression of SIRT1 protein in the diabetic group (0.060 ± 0.028) and the treatment group (0.073 ± 0.026) was significantly decreased,and the overall difference among the three groups was statistically significant (F =1 310.663,P =0.000),while the differences between each two groups were also statistically significant (all P =0.000).The expression levels of p38 MAPK and Caspase-3 were increased in diabetic group (1.121 ± 0.082,0.266 ± 0.005) and treatment group (0.574 ± 0.012,0.190 ±0.060) respectively,and the overall difference and pairwise comparison in the three groups approached statistically significance (all P =0.000,0.000).Conelusion Up-regulation of SIRT1,can inhibit the apoptosis of RGCs,and protect RGCs against apoptosis in rat model of diabetic retinopathy,which may be correlated with the downregulation of p38 MAPK signal pathway.关键词
糖尿痛视网膜病变/沉默信息调节因子相关酶l/p38 MAPK信号通路/视网膜神经节细胞Key words
diabetic retinopathy/sirtuin type 1/p38 mitogen-activated protein kinase pathway/retina ganglion cells分类
医药卫生引用本文复制引用
钱道卫,廖燕秋,李远存,郭海科,伍岚..沉默信息调节因子相关酶1(SIRT1)调控p38MARK信号通路对糖尿病视网膜病变大鼠视网膜神经节细胞的保护作用及机制[J].眼科新进展,2017,37(10):926-930,5.基金项目
深圳市科技计划创新项目(编号:JCYJ20140416095712-709) （编号:JCYJ20140416095712-709）
深圳市坪山新区卫生科研项目(编号:201517)Science and Technology Innovation Plan of Shenzhen (No:JCYJ20140416095712709) （编号:201517）
Health Plan of Scientific Research of Pingshan New District of Shenzhen (No.:201517) （No.:201517）
