齐墩果酸对糖尿病大鼠视网膜氧化应激反应和视网膜神经节细胞损伤的影响  

Effects of oleanolic acid on retinal oxidative stress response and retinal ganglion cell injury in diabetic rats

作　　者：梁福珍 樊芳[2] 毕萌 季彤 李瀚邦 马晓婷 刘宇[1] 胡志娟[4] 贾志旸[2] LIANG Fuzhen;FAN Fang;BI Meng;JI Tong;LI Hanbang;MA Xiaoting;LIU Yu;HU Zhijuan;JIA Zhiyang(Hebei Medical University,Shijiazhuang 050017,Hebei Province,China;Department of Ophthalmology,Hebei General Hospital,Shijiazhuang 050051,Hebei Province,China;North China University of Science and Technology,Tangshan 063210,Hebei Province,China;Department of Nephrology,Hebei General Hospital,Shijiazhuang 050051,Hebei Province,China)

机构地区：[1]河北医科大学,河北省石家庄市050017 [2]河北省人民医院眼科,河北省石家庄市050051 [3]华北理工大学,河北省唐山市063210 [4]河北省人民医院肾内科,河北省石家庄市050051

出　　处：《眼科新进展》2023年第7期526-529,共4页Recent Advances in Ophthalmology

摘　　要：目的 探讨齐墩果酸对糖尿病大鼠视网膜氧化应激反应和视网膜神经节细胞(RGC)损伤的影响。方法 取6周龄健康清洁级雄性SD大鼠30只,将大鼠随机分为对照组、糖尿病组和齐墩果酸组,每组10只。对照组大鼠给予鼠维持饲料喂养,糖尿病组和齐墩果酸组给予高脂饲料喂养。4周后,按照35 mg·kg^(-1)的剂量给予糖尿病组和齐墩果酸组大鼠腹腔内注射链脲佐菌素,对照组注射相应体积的柠檬酸钠缓冲液。次日尾静脉采血,大鼠空腹血糖≥11.1 mmol·L^(-1)说明造模成功。剔除2只造模失败的大鼠,最终对照组10只大鼠,糖尿病组9只,齐墩果酸组9只。齐墩果酸组大鼠每天给予100 mg·kg^(-1)齐墩果酸灌胃,对照组及糖尿病组每天给予等量的溶剂灌胃。干预8周后处死大鼠,摘取双侧眼球。分离大鼠左眼视网膜,检测大鼠视网膜组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。将大鼠右侧眼球固定后,石蜡包埋、切片,HE染色观察视网膜组织形态,免疫组织化学染色计算RGC密度并检测核因子红细胞2相关因子2(Nrf2)及血红素加氧酶1(HO-1)蛋白表达情况。结果 糖尿病组大鼠视网膜组织SOD活性低于对照组,齐墩果酸组大鼠视网膜组织SOD活性高于糖尿病组,差异均有统计学意义(均为P<0.05)。糖尿病组大鼠视网膜组织MDA含量高于对照组,齐墩果酸组大鼠视网膜组织MDA含量低于糖尿病组,差异均有统计学意义(均为P<0.05)。与对照组相比,糖尿病组大鼠视网膜变薄,结构疏松,内核层和外核层细胞排列紊乱,外丛状层连续性差;与糖尿病组相比,齐墩果酸组大鼠视网膜结构较清晰,细胞排列较整齐。糖尿病组大鼠视网膜组织RGC密度小于对照组,齐墩果酸组大鼠视网膜组织RGC密度大于糖尿病组,差异均有统计学意义(均为P<0.05)。糖尿病组大鼠视网膜组织Nrf2及HO-1染色阳性的平均光密度均高于对照组,齐墩果酸组大鼠�Objective To investigate the effects of oleanolic acid on retinal oxidative stress response and retinal ganglion cell(RGC)injury in diabetic rats.Methods Thirty 6-week-old healthy male SD rats were selected and randomly divided into the control group,diabetic group,and oleanolic acid group,with 10 rats in each group.Rats in the control group were fed maintenance diets,while rats in the diabetic and oleanolic acid groups were fed high-fat diets.After 4 weeks,the rats in diabetic and oleanolic acid groups were intraperitoneally injected with streptozotocin at a dose of 35 mg·kg^(-1),while the rats in the control group were injected with the same amount of sodium citrate buffer.Blood was collected from the tail vein on the following day.If the fasting blood glucose level was greater than or equal to 11.1 mmol·L^(-1),it indicated successful modeling.Two rats that failed in modeling were excluded,and finally,10 rats were in the control group,9 rats in the diabetic group,and 9 rats in the oleanolic acid group.The rats in the oleanolic acid group were given 100 mg·kg^(-1) oleanolic acid by gavage daily,and the rats in the control and diabetic groups were given an equal amount of solvent by gavage daily.After 8 weeks of intervention,the rats were executed,and both eyes were removed.The retinas in the left eyes were isolated and used to measure the superoxide dismutase(SOD)activity and malondialdehyde(MDA)content.The right eyes were fixed,paraffined,sectioned,and stained with hematoxylin&eosin to analyze the retinal histomorpho\|logy.Immunohistochemical staining was performed to measure the RGC density and the expression of nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase 1(HO-1).Results The SOD activity in the diabetic group was lower than that in the control and oleanolic acid groups(both P<0.05).The MDA content in the diabetic group was higher than that in the control and oleanolic acid groups(both P<0.05).Compared with the control group,the retinas of rats in the diabetic group were thinner and l

关 键 词：齐墩果酸 Nrf2信号通路 糖尿病视网膜病变 氧化应激 视网膜神经节细胞 

分 类 号：R774[医药卫生—眼科]