他克莫司通过调节Nrf2-Keap1信号通路改善大鼠肾病综合征中的氧化应激反应  

Tacrolimus Ameliorates Oxidative Stress in Rats with Nephrotic Syndrome by Regulating Nrf2-Keap1 Signal Pathway

作　　者：孙德胤 孙艺[1] 郑华[1] SUN Deyin;SUN Yi;ZHENG Hua(Department of Nephrology,Central Hospital Affiliated to Shenyang Medical College,Shenyang 110024)

机构地区：[1]沈阳医学院附属中心医院肾内科,沈阳110024

出　　处：《中国中西医结合肾病杂志》2022年第4期296-299,I0002,共5页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：沈阳医学院科技基金资助项目(No.20181007)。

摘　　要：目的:探讨他克莫司对肾病综合征模型大鼠的保护作用及相关作用机制。方法:采用尾静脉一次性注射阿霉素(5 mg/kg)的方法构建大鼠肾病综合征模型,将大鼠随机分为假手术组、ADR组和FK506组;对各组大鼠进行组织病理学的检测;采用AU5800生化分析仪检测各组大鼠的24 h尿蛋白含量、血清中的血肌酐和尿素氮含量;采用ELISA法检测TNF-α、IL-10、IL-1β以及SOD、MDA、ROS的水平变化;应用Western Blot法检测Nrf2、Keap1、ARE的表达状况。结果:他克莫司可以显著降低肾脏组织损伤;降低炎症的相关指标的表达水平;降低MDA、ROS的表达水平,增强SOD的活性;促进Nrf2、ARE的表达水平,抑制Keap1的表达。结论:他克莫司能够改善肾病综合征模型大鼠肾功能,改善模型大鼠氧化应激状态,其作用机制可能与活化Nrf2-Keap1信号通路有关。Objective:To investigate the protective effect of Tacrolimus on nephrotic syndrome model and its mechanism.Methods:Nephrosis was induced by single intravenous injection of ADR(5 mg/kg)and randomly divided into Sham group,ADR group and FK506 group.The histopathology of rats in each group was detected;the 24-hour urinary protein,serum creatinine and urea nitrogen content were detected by AU5800 biochemical analyzer;the levels of TNF-α,IL-10,IL-1β,SOD,MDA and ROS were detected by ELISA;the expression of Nrf2,Keap1 and ARE detected by Western blot.Results:Tacrolimus can significantly reduce the renal tissue injury;reduce the expression level of inflammation;reduce the expression level of MDA and ROS,enhance the activity of SOD;promote the expression level of Nrf2 and ARE,inhibit the expression of Keap1.Conclusion:Tacrolimus can improve the renal function and oxidative stress of nephrotic syndrome,and its mechanism may be related to the activation of Nrf2-Keap1 signal pathway.

关 键 词：他克莫司 肾病综合征 Nrf2-Keap1信号通路 氧化应激 

分 类 号：R692[医药卫生—泌尿科学]