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Keap1-Nrf2/ARE信号通路介导黄连素调节氧化应激改善小鼠糖尿病肾病 被引量:10

Effect of Berberine on Diabetic Nephropathy via Keap1-Nrf2/ARE Pathway Resist Oxidative Stress
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摘要 目的采用小鼠糖尿病肾病的模型并结合氧化应激,探讨黄连素改善糖尿病并发症中肾脏病变的作用和机制。方法将糖尿病肾病(DN)小鼠分别灌胃给予二甲双胍(0.2g/kg)、黄连素低、中、高剂量(0.036、0.072、0.144g/kg)8周。检测血清中相应指标;检测肾脏中活性氧(ROS)及超氧化物歧化酶(SOD)水平,Kelch样环氧氯丙烷相关蛋白-1(Keap1)、核因子E2相关因子2(Nrf2)及还原型辅酶Ⅱ氧化酶4(NOX4)蛋白表达;检测24h尿蛋白等指标。结果黄连素可显著降低DN小鼠血糖,增加胰岛素分泌,降低24h尿蛋白、血清尿素氮和肌酐、上调SOD和Nrf2水平,下调ROS、Keap1及NOX4水平。结论黄连素具有改善小鼠糖尿病肾病的作用,且中、高剂量作用较优,其相关机制可能与调控Keap1-Nrf2/ARE信号通路,从而改善氧化应激有关。 Objective In the study, the effect of berberine on Diabetic Nephropathy (DN) via oxidative stress was studied. Meth- ods The DN model mice was administered with metformin (0.2g/kg), low - dose berberine (0. 036 g/kg), middle - dose berberine (0. 072g/kg) and high- dose berberine (0. 144g/kg) for 8 weeks. After that, the fasting glucose, insulin, serum creatinine, urea nitrogen, Reactive Oxidative Species ( ROS), Superoxide Dismutase (SOD) , Kelch - like ECH - associated protein 1 ( Keapl ) ,Nuclear factor (erythroid - derived 2) - like 2 (Nrf2) and NADPH oxidase 4 (NOX4) , 24h urine protein, etc were measured. Results Berberine could significantly decrease the fasting blood glucose levels, increase the insulin production, and reduce the levels of 24 h urine protein, serum urea nitrogen, creatinine, improve SOD and Nrf2, decrease ROS, Keapland NOX4. Conclusion Berberine has the protactive effects in DN mice via the Keap - Nrf2/ARE pathway, and middle/high - dose berberine was much better. The mechanism may be related to the alleviated of the oxidative stress.
作者 盛冬琴
出处 《医学研究杂志》 2017年第8期176-180,共5页 Journal of Medical Research
关键词 黄连素 糖尿病肾病 氧化应激 Keapl-Nrf2/ARE信号通路 Berberine Diabetic nephropathy Oxidative stress Keapl -Nrf2/ARE pathway
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