白藜芦醇对糖尿病肾病小鼠肾脏氧化应激及肾组织Nrf2通路蛋白表达的影响  

Effects of resveratrol on oxidative stress and Nrf2 signal pathway expression in kidney of mice with diabetic nephropathy

作　　者：高丝娜 李英 迟雁青 刘翠红[1] 曹义甫 GAO Sina;LI Ying;CHI Yanqing;LIU Cuihong;CAO Yifu(Shijiazhuang Third Hospital, Shijiazhuang 050000, China)

机构地区：[1]石家庄市第三医院,石家庄050000 [2]河北医科大学第三医院

出　　处：《山东医药》2019年第11期44-47,52,共5页Shandong Medical Journal

摘　　要：目的观察白藜芦醇对糖尿病肾病(DN)小鼠肾脏氧化应激及核转录因子(NF) E2相关因子2(Nrf2)信号通路蛋白表达的影响,探讨白藜芦醇对DN小鼠肾脏的保护作用及其机制。方法选择单侧肾切除的雄性CD-1小鼠,分为正常对照组、白藜芦醇对照组、模型组、白藜芦醇治疗组各10只。模型组与白藜芦醇治疗组通过腹腔注射链脲佐菌素(STZ)制备DN模型,正常对照组与白藜芦醇对照组注射等体积枸橼酸缓冲液。造模后,白藜芦醇对照组与白藜芦醇治疗组给予白藜芦醇5 mg/(kg·d)灌胃,正常对照组与模型组给予相同体积的羧甲基纤维素溶液灌胃。于造模成功后第8周收集各组24 h尿液,股动脉取血,检测肾功能相关指标,包括24 h尿蛋白定量(UP)、血肌酐(Scr)、尿素氮(BUN)。取肾皮质匀浆100μL,采用硫代巴比妥酸法测定丙二醛(MDA)含量,黄嘌呤氧化酶法测定总超氧化物歧化酶(T-SOD)活性。切取部分肾脏,采用免疫组化染色法及Western blotting法检测肾组织Nrf2、血红素氧合酶1(HO-1)蛋白表达。结果与正常对照组比较,模型组UP、Scr、BUN均升高;与模型组比较,白藜芦醇治疗组UP、Scr、BUN均下降(P <0. 01或0. 05)。与模型组比较,白藜芦醇治疗组MDA含量降低、T-SOD活性升高(P均<0. 05)。Nrf2、HO-1蛋白在正常对照组和白藜芦醇对照组均仅见少量表达,模型组Nrf2、HO-1蛋白表达均较正常对照组增加,白藜芦醇治疗组蛋白表达均较模型组进一步增加(P均<0. 01)。结论 DN小鼠肾脏存在明显的氧化应激损伤,白藜芦醇可能通过激活Nrf2-ARE通路,减轻DN小鼠肾脏的氧化应激损伤,发挥肾脏保护作用。Objective To observe the effects of resveratrol on oxidative stress and protein expression of the NF-E2-related factor-2/antioxidant response element (Nrf2/ARE) signal pathway in kidney of mice with diabetic nephropathy (DN) and to explore the protection of resveratrol for the renal tissues of DN mice. Methods Uninephrectomized male CD-1 mice were randomly divided to four groups: the normal control group, resveratrol control group, model group, and resveratrol-treated diabetic group. The mice of the diabetic group and resveratrol-treated diabetic group received singal intraperitoneal injection of streptozotocin (STZ) to make the type 1 diabetic models. The mice in the normal control group and resveratrol control group were injected with equal volume of citric acid buffer. Then the mice in the resveratrol control group and resveratrol-treated diabetic group were intragastrically administered 5 mg/(kg.d) resveratrol, while the normal control group and the model group were intragastrically administered the equal volume of carboxymethyl cellulose solution. At week 8 after successful modeling, 24 h urine albumin (UP), serum creatinine (Scr), blood urea nitrogen (BUN), the content of malonaldehyde (MDA) and the activity of total superoxide dismutase (T-SOD) of renal cortex were detected. Meanwhile, the expression of heme oxygenase-1 (HO-1) and Nrf2 was detected by immunohistochemistry and Western blotting. Results Compared with the normal control group, the UP, Scr, and BUN of the model group increased. Compare with the model group, the Scr, BUN and UP of the resveratrol-treated diabetic group decreased ( P <0.01 or P <0.05). Compare with the model group, the content of MDA decreased and the activity of T-SOD increased in the renal cortex of the resveratrol-treated diabetic group ( P <0.05). The expression of Nrf2 and HO-1 protein in the normal control group and resveratrol control group was only a small amount;the expression of Nrf2 and HO-1 protein in the model group was higher than that in the normal control group;t

关 键 词：氧化应激 NF-E2相关因子 血红素氧合酶1 白藜芦醇 糖尿病肾病 小鼠 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]