白藜芦醇介导Nrf2/ARE信号通路对大鼠草酸钙肾结石模型的抗氧化损伤作用  

Antioxidant damage of resveratrol via Nrf2/ARE signaling pathway on rat calcium oxalate stone models

作　　者：阿不都赛买提·艾力 辛瑞平 阿斯木江·阿不拉[2] 郭明月 关永志 陈庆虎 木拉提·马合木提[3] ABUDUSAIMAITI Ali;XIN Ruiping;ASIMUJIANG Abula;GUO Mingyue;GUAN Yongzhi;CHEN Qinghu;MULATI Mahemuti(Department of Urology,Yilihasake Autonomy State Xinhua Hospital,Yili 835000;Department of Urology,The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054;Department of Urology,The Second Affiliated Hospital of Xinjiang Medical University,Urumqi 830063,China)

机构地区：[1]伊犁哈萨克自治州新华医院泌尿外科,新疆伊宁835000 [2]新疆医科大学第一附属医院泌尿外科,新疆乌鲁木齐830054 [3]新疆医科大学第二附属医院泌尿外科,新疆乌鲁木齐830063

出　　处：《现代泌尿外科杂志》2021年第9期785-789,791,共6页Journal of Modern Urology

基　　金：国家自然科学基金项目(No.81760128);自治区卫健委青年科技人才项目(No.WJWY-201943)。

摘　　要：目的探讨白藜芦醇(Res)在大鼠草酸钙肾结石模型中的抗氧化作用。方法将24只SD大鼠随机分为对照组、结石模型组和结石模型+Res干预组,每组8只。结石组给予自由饮水并用乙二醇+氯化铵溶液灌胃(2mL/d)法制备草酸钙结石模型,干预组在结石模型基础上加用Res灌胃(每日200mg/kg)。28d造模完成后采集肾组织标本,用HE染色法比较各组肾脏病理改变及草酸钙结晶的沉积情况并检测肾组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽(GSH)含量;RT-PCR法检测核因子E2相关因子2(Nrf2)mRNA表达水平;Western blot法检测Nrf2蛋白表达水平。结果①肾组织病理结果:肾组织与对照组比较,结石模型组大鼠肾组织HE染色切片中可见肾小管的病理性改变并大量结晶形成(P<0.05);与结石模型组比较,结石模型+Res干预组肾小管扩张不明显,炎细胞浸润以及管腔内草酸钙晶体明显减少(P<0.05)。②肾组织氧化应激物水平:与对照组比较,结石模型组SOD、CAT和GSH含量降低,MDA含量升高(P<0.05);与结石模型组比较,结石模型+Res干预组SOD、CAT和GSH含量显著升高,MDA含量显著降低(P<0.05)。③肾组织Nrf2蛋白水平:与对照组比较,结石模型组Nrf2mRNA和Nrf2蛋白表达量降低(P<0.05);与结石模型组比较,结石模型组+Res干预组Nrf2mRNA和蛋白表达量明显升高(P<0.05)。结论Res通过其抗氧化作用抑制/延缓了草酸钙晶体对大鼠肾小管上皮细胞的损伤及粘附,此作用可能与Nrf2/ARE信号通路有关。Objective To explore the antioxidant effects of resveratrol(Res)on the calcium oxalate stone models in rats.Methods A total of 24 SD rats were randomly divided into 3 groups:control group,stone model group and stone model+Res intervention group,with 8 rats in each group.The rats in control group were permitted to drink water freely,while the rats in stone model group were intragastrically given glycol and ammonium chloride solution of 2 mL/d on the basis of free water intake.The rats in stone model+Res intervention group were intragastrically given resveratrol solution of 200 mg·kg^(-1)·d^(-1) after 8 hour gavage.After 28 days,the kidney tissues were collected.The pathological changes and calcium oxalate deposition were observed with HE staining.The levels of malondialdehde(MDA),superoxide dismutase(SOD),catalase(CAT)and glutathione(GSH)in the renal tissues were measured.The mRNA expression of Nrf2 was detected with RT-qPCR,and the protein expression of Nrf2 was detected with Western blot.Results①Renal histopathological resuts:Compared with the control group,the stone model group showed obviously expanded renal tubules and a large amount of crystal formation;reduced levels of SOD and GSH,but increased MDA;reduced mRNA and protein expressions of Nrf2(P<0.05).②levels of oxidants and Nrf2 protein level in renal tissue:Compared with the stone model group,the stone model+Res intervention group showed insignificant dilatation of renal tubules,but significantly reduced infiltration of inflammatory cells and formation of crystals;increased SOD,CAT and GSH,but decreased MDA;increased mRNA and protein expressions of Nrf2(P<0.05).Conclusion Resveratrol inhibits/delays the damage and adhesion of calcium oxalate nephrolithiasis to the renal tubular epithelial cells of rats through its antioxidant effects,which may be related to the signaling pathway of Nrf2/ARE.

关 键 词：白藜芦醇 草酸钙肾结石 信号通路 氧化应激 

分 类 号：R692.4[医药卫生—泌尿科学]