白藜芦醇通过Nrf2/HO-1通路对高糖诱导的视网膜神经节细胞损伤的保护作用机制  

The Protective Mechanism of Resveratrol Against High Glucose-Induced Retinal Ganglion Cell Injury via Nrf2/HO-1 Pathway

作　　者：胡寅 崔莎 李卓君 胡琴[2] 邱志方[2] Hu Yin;Cui Sha;Li Zhuojun;Hu Qin;Qiu Zhifang(Affiliated Hospital of Hubei University of Arts and Sciences Xiangyang Central Hospital,Xiangyang 441003,China;Xiangyang Aier Ophthalmic Hospital,Xiangyang 441003,China)

机构地区：[1]湖北文理学院附属医院\襄阳市中心医院,襄阳441003 [2]襄阳爱尔眼科医院,襄阳441003

出　　处：《世界科学技术-中医药现代化》2022年第12期4681-4689,共9页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：襄阳市科学技术局科技计划项目(2018sh82):白藜芦醇通过Nrf2/HO-1通路对高糖诱导的视网膜神经节细胞损伤的影响研究;负责人:胡寅。

摘　　要：目的 探讨白藜芦醇通过Nrf2/HO-1通路对高糖诱导的视网膜神经节细胞损伤的影响。方法将野生型C57BL/6小鼠随机分为3组:对照组、高糖组和RES组,每组20只。Nrf2敲除的C57BL/6小鼠为RES+Nrf2敲除组,20只。建立糖尿病视网膜病变小鼠模型,HE染色观察RES对视网膜组织的影响;流式细胞仪检测视网膜神经节细胞凋亡率;ELISA法检测超氧化物歧化酶(SOD)、丙二醛(MDA)和8-羟基脱氧鸟苷(8-OHdG)的含量;Western blot检测Nrf2和Ho-1蛋白表达。结果 与高糖组相比,RES组可以减轻高糖诱导引起的损伤;而RES+Nrf2敲除组较RES组相比,视网膜神经节细胞层(GCL)、内核层(INL)有所减少,外核层(ONL)厚度有所降低。RES组视网膜厚度显著高于高糖组(P<0.05),RES+Nrf2敲除组视网膜厚度相对低于RES组(P<0.05)。RES组中的神经节数量明显高于高糖组(P<0.05),RES+Nrf2敲除组中的神经节数量显著低于RES组(P<0.05)。RES组中的凋亡率明显低于高糖组(P<0.05),RES+Nrf2敲除组中的凋亡率显著高于RES组(P<0.05)。高糖组中的Bax和Cleaved Caspase3蛋白表达明显高于对照组(P<0.05),RES组中的Bax和Cleaved Caspase3蛋白表达明显低于高糖组(P<0.05),RES+Nrf2敲除组中的Bax和Cleaved Caspase3蛋白表达显著高于RES组(P<0.05);而高糖组中的Bcl2蛋白表达明显低于对照组(P<0.05),RES组中的Bcl2蛋白表达明显高于高糖组(P<0.05),RES+Nrf2敲除组中的Bcl2蛋白表达显著低于RES组(P<0.05)。RES组中的SOD水平明显高于高糖组(P<0.05),RES+Nrf2敲除组中的SOD水平显著低于RES组(P<0.05);而RES组中的MDA和8-OHdG水平明显低于高糖组(P<0.05),RES+Nrf2敲除组中的MDA和8-OHdG水平显著高于RES组(P<0.05)。此外,RES组中Nrf2和Ho-1的蛋白表达明显高于高糖组(P<0.01),RES+Nrf2敲除组Nrf2和Ho-1的蛋白表达显著低于RES组(P<0.05)。结论 白藜芦醇对糖尿病性视网膜病变小鼠视网膜和神经节细胞具有一定的保护作用,白藜芦醇通过激活Nrf2�Objective To investigate the effect of resveratrol on retinal ganglion cell injury induced by high glucose through nuclear factor eryth6roid 2-related factor 2(Nrf2)/Heme Oxygenase-1(HO-1) pathway.Methods The wildtype C57BL/6 mice were randomly divided into 3 groups,the control group,the high glucose group and the RES group,with 20 mice in each group.The Nrf2 knockout C57BL/6 mice were the RES+Nrf2 knockout group,with 20 mice.A mouse model of diabetic retinopathy was established.HE staining was used to observe the effect of RES on retinal tissue;flow cytometry was used to detect the apoptosis rate of retinal ganglion cells;and ELISA was used to detect superoxide dismutase(SOD),malondialdehyde(MDA) and the content of 8-hydroxydeoxyguanosine(8-OHdG) was detected by Western blot to detect the expression of Nrf2 and Ho-1 protein.Results Compared with the high glucose group,the RES group can reduce the damage induced by high glucose;and the RES+Nrf2 knockout group has a decrease in the retinal ganglion cell layer(GCL) and inner nuclear layer(INL) compared with the RES group,the thickness of the outer nuclear layer(ONL) was reduced.The retinal thickness of the RES group was significantly higher than that of the high glucose group(P<0.05),and the retinal thickness of the RES+Nrf2 knockout group was relatively lower than that of the RES group(P<0.05).The number of ganglia was significantly higher than that in the high glucose group(P<0.05),and the number of ganglia in the RES+Nrf2 knockout group was significantly lower than that in the RES group(P<0.05).The apoptosis rate in the RES group was significantly lower than that in the high glucose group(P<0.05),the apoptosis rate in the RES+Nrf2 knockout group was significantly higher than that in the RES group(P<0.05).The protein expression of Bax and Cleaved Caspase3 in the high glucose group were significantly higher than that of the control group(P<0.05),the protein expression of Bax and Cleaved Caspase3 in the RES group were significantly lower than that of the high gluco

关 键 词：白藜芦醇 核因子E2相关因子2 血红素氧合酶1 高糖 视网膜神经节细胞损伤 

分 类 号：R285.5[医药卫生—中药学]