柚皮素对糖尿病视网膜病变大鼠氧化损伤、细胞凋亡及Nrf2-ARE的影响  

The effects of Naringenin on oxidative damage,apoptosis and Nrf2-ARE in rats with diabetic retinopathy

作　　者：徐辉勇[1] 陈金鹏[1] 章剑[1] XU Hui-yong;CHEN Jin-peng;ZHANG Jian(Department of Ophthalmology,Ezhou Central Hospital,E'zhou Hubei 436000,China)

机构地区：[1]鄂州市中心医院眼科

出　　处：《临床和实验医学杂志》2020年第2期128-132,共5页Journal of Clinical and Experimental Medicine

基　　金：湖北省科技计划自然科学基金面上项目(编号:2015CFB568)

摘　　要：目的探讨柚皮素对糖尿病视网膜病变(DR)大鼠氧化损伤、细胞凋亡及核因子E2相关因子2(Nrf2)-抗氧化反应元件(ARE)的影响。方法随机数字表法将健康雄性SD大鼠分为空白对照组、模型组、阳性对照组、低剂量柚皮素组、中剂量柚皮素组、高剂量柚皮素组。采用腹腔注射链脲佐菌素(STZ)法建立DR大鼠模型。阳性对照组灌胃150 mg·kg^-1·d^-1羟苯磺酸钙,低、中、高剂量柚皮素组分别灌胃25 mg·kg^-1·d^-1、50 mg·kg^-1·d^-1、100 mg·kg^-1·d^-1柚皮素,空白对照组和模型组灌胃1%二甲基亚砜(DMSO),连续灌胃60 d。取各组大鼠视网膜组织,试剂盒检测丙二醛(MDA)含量、超氧化物歧化酶(SOD)和谷胱甘肽还原酶(GSH-Px)活力,TUNEL染色法检测视网膜组织的神经节细胞凋亡情况,Western blot法检测核因子E2相关因子2(Nrf2)、醌氧化还原酶-1(NQO1)和血红素加氧酶-1(HO-1)蛋白表达。结果与空白对照组比,模型组大鼠视网膜组织MDA含量、细胞凋亡指数显著升高(P<0.05),SOD和GSH-Px活力、Nrf2、HO-1、NQO1蛋白表达显著降低(P<0.05)。与模型组比,中、高剂量柚皮素组和阳性对照组大鼠视网膜组织MDA含量、细胞凋亡指数显著降低(P<0.05),SOD和GSH-Px活力、Nrf2、HO-1、NQO1蛋白表达显著降低显著升高(P<0.05),但低剂量组各指标均无显著差异(P>0.05)。结论柚皮素可能通过激活Nrf2-ARE信号通路降低糖尿病视网膜病变大鼠氧化应激损伤,其作用呈剂量依赖性。Objective To investigate the effects of naringenin on oxidative damage,apoptosis and Nrf2-ARE in diabetic retinopathy(DR)rats.Methods Healthy male SD rats were randomly divided into blank control group,model group,positive control group,low-dose naringenin group,medium-dose naringenin group and high-dose naringenin group.DR rat model was established by intraperitoneal injection of streptozotocin(STZ).The positive control group was intragastrically administered with 150 mg·kg^-1·d^-1 calcium hydroxybenzenesulfonate.The low,medium and high doses of naringenin group were intragastrically administered with 25 mg·kg^-1·d^-1,50 mg·kg^-1·d^-1,100 mg·kg^-1·d^-1 naringenin respectively,and the blank control group and model group were intragastrically administered with 1%DMSO for 60 days.Retinal tissues of rats in each group were taken,the content of MDA and the activities of SOD and GSH-Px were detected by the kits;the apoptosis of gangliocytes in retinal tissues was detected by TUNEL staining;the expressions of Nrf2,NQO1,and HO-1 proteins were detected by Western blot.Results Compared with the blank control group,the content of MDA and apoptotic index in retina tissues of rats in model group increased significantly(P<0.05),SOD and GSH-Px activities,Nrf2,HO-1,and NQO1 protein expressions decreased significantly(P<0.05).Compared with model group,the content of MDA and apoptotic index in retina tissues of rats in middle and high dose naringenin groups and positive control group decreased significantly(P<0.05),SOD and GSH-Px activities,Nrf2,HO-1,and NQO1 protein expressions were increased significantly(P<0.05).However,there was no significant difference in each index in the low-dose group(P>0.05).Conclusion Naringenin may reduce oxidative stress injury in diabetic retinopathy rats by activating Nrf2-ARE signal pathway dose-dependent.

关 键 词：大鼠 糖尿病视网膜病变 柚皮素 氧化损伤 细胞凋亡 Nrf2-ARE 

分 类 号：R285.5[医药卫生—中药学]