亚硒酸钠对造影剂致急性肾损伤大鼠肾功能及Nrf2/ARE通路的影响  

Effects of sodium selenite on renal function in rats with contrast-induced acute kidney injury and the Nrf2/ARE signaling pathway

作　　者：向海燕 李根 张云 吴艳 洪苑浩 徐亚苓 XIANG Haiyan;LI Gen;ZHANG Yun(Department of Nephrology,the Sixth Hospital of Wuhan(Affiliated Hospital of Jianghan University),Hubei,Wuhan 430014,China)

机构地区：[1]湖北省武汉市第六医院、江汉大学附属医院肾内科,430014

出　　处：《河北医药》2024年第19期2909-2913,2918,共6页Hebei Medical Journal

基　　金：湖北省教育厅指导性资助项目(编号:B2018086);湖北省卫健委青年人才项目(编号:wj2019H151);江汉大学附属医院博士专项(编号:K20230327006)。

摘　　要：目的 探讨亚硒酸钠(SS)对造影剂诱导的急性肾损伤(CIAKI)大鼠肾功能及核因子E2相关因子2(Nrf2)/抗氧化反应元件(ARE)通路的影响。方法 将SPF级雄性SD大鼠按照随机数字表分为对照组、模型组、SS低、中、高剂量组(0.1、0.3、0.5 mg/kg)、抑制剂组(10 mg/kg Nrf2/ARE通路抑制剂ATRA),每组12只,除对照组外,其他各组建立造影剂急性肾损伤大鼠模型。造模前3 d和造模后3 d,各组给予相应干预措施。全自动生化分析仪检测肾功能指标血尿素氮(BUN)、血清肌酐(Scr);HE染色观察肾组织病理学变化;荧光探针法检测肾组织中活性氧(ROS);试剂盒检测谷胱甘肽过氧化物酶(GSH-Px)水平;免疫组化方法检测Nrf2、肾损伤分子-1(KIM-1)表达;qRT-PCR和Western blot检测Kelch样ECH相关蛋白1(Keap1)、血红素加氧酶1(HO-1)、醌氧化还原酶1(NQO1)mRNA及蛋白表达。结果 与对照组比较,模型组大鼠肾组织病理损伤严重,肾小管细胞坏死和脱落、肾小管上皮细胞肿胀和空泡变性,肾间质有明显的炎性细胞浸润,BUN、Scr、ROS水平、肾小管病理损伤评分,KIM-1阳性表达、Keap1 mRNA及蛋白表达显著升高,GSH-Px水平、细胞核内Nrf2阳性表达、HO-1、NQO1 mRNA及蛋白表达显著降低(P<0.05);与模型组比较,SS低、中、高剂量组大鼠肾组织病理损伤依次减轻,肾小管上皮细胞肿胀和空泡变性程度改善,炎性细胞浸润显著减轻,BUN、Scr、ROS水平、肾小管病理损伤评分、KIM-1阳性表达、Keap1 mRNA及蛋白表达显著降低,GSH-Px水平、细胞核内Nrf2阳性表达、HO-1、NQO1 mRNA及蛋白表达显著升高(P<0.05);与SS高剂量组比较,抑制剂组大鼠肾脏病理损伤加重,上述指标变化均显著逆转(P<0.05)。结论 SS通过激活Nrf2/ARE通路,抑制氧化应激反应,改善CIAKI大鼠肾功能,从而起肾保护的作用。Objective To investigate the effects of sodium selenite(SS)on renal function in contrast-induced acute kidney injury(CIAKI)rats and the nuclear factor erythroid-2 related factor 2(Nrf2)/antioxidant responsive element(ARE)signaling pathway.Methods Male Sprague-Dawley(SD)rats in the specific-pathogen free(SPF)grade were randomly grouped into control group,model group,low-dose SS group(0.1mg/kg),medium-dose SS group(0.3mg/kg),high-dose SS group(0.5mg/kg),and inhibitor group(10mg/kg Nrf2/ARE pathway inhibitor all-trans retinoic acid[ATRA]),with 12 rats in each group.Except for rats in the control group,CIAKI modeling was performed in the remaining groups.Three days before and three days after modeling,each group was given corresponding intervention measures.Fully automated biochemical analyzer was used to detect renal function indicators,such as blood urea nitrogen(BUN)and serum creatinine(Scr).Hematoxylin and eosin(H&E)staining was applied to observe pathological changes in renal tissues.Fluorescence probe method was applied to detect reactive oxygen species(ROS)in renal tissues.Relative level of glutathione peroxidase(GSH-Px)was measured using a commercial kit.Immunohistochemical staining was applied to detect the positive expressions of Nrf2 and kidney injury molecule-1(KIM-1).Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot were applied to detect the mRNA and protein expressions of Kelch like ECH related protein 1(Keap1),heme oxygenase 1(HO-1),and quinone oxidoreductase 1(NQO1),respectively.Results Compared with those of control group,rats in the model group presented severe pathological damages to renal tissues,necrosis and shedding of renal tubular cells,swelling and vacuolar degeneration of renal tubular epithelial cells,inflammatory cell infiltration in renal interstitium,significantly higher BUN,Scr,ROS,renal tubular pathological injury score,positive expression of KIM-1,mRNA and protein expressions of Keap1,and significantly lower GSH-Px,positive expression of nuclear Nrf2,mRNA and

关 键 词：肾损伤 急性 亚硒酸钠 肾功能 核因子E2相关因子2 抗氧化反应元件 

分 类 号：R692[医药卫生—泌尿科学]