器官移植2026，Vol.17Issue(5)：772-782,11.DOI:10.12464/j.issn.1674-7445.2026099
黄芪甲苷通过激活Nrf2/HO-1通路抑制NLRP3介导的焦亡缓解肾缺血-再灌注损伤
Astragaloside Ⅳ inhibited NLRP3-mediated pyroptosis and alleviated renal ischemia-reperfusion injury by activating the Nrf2/HO-1 pathway
摘要
Abstract
Objective To investigate the effect of astragaloside Ⅳ(AS-Ⅳ)on renal ischemia-reperfusion injury(RIRI)and its specific mechanism.Methods Forty-eight rats were randomly divided into 6 groups,with 8 rats in each group:sham operation group(Sham group),RIRI group,RIRI+AS-Ⅳ(10 mg/kg)group,RIRI+AS-Ⅳ(20 mg/kg)group,RIRI+AS-Ⅳ(40 mg/kg)group and RIRI+AS-Ⅳ+Brusatol group[Brusatol is a nuclear factor E2-related factor 2(Nrf2)inhibitor].Serum creatinine(Scr)and blood urea nitrogen(BUN)levels of rats were detected using an automatic biochemical analyzer;the pathological damage degree of rats kidney tissue was evaluated by hematoxylin-eosin staining and scored;the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in rats serum,and interleukin(IL)-1βand IL-18 in rats kidney tissue were detected by enzyme-linked immunosorbent assay;the degree of cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling;real-time fluorescence quantitative polymerase chain reaction and Western blotting were used to determine the messenger RNA(mRNA)and protein levels of Nrf2/heme oxygenase-1(HO-1)signaling pathway and cell pyroptosis regulatory factors in rats kidney tissue.Results Compared with the Sham group,the BUN and Scr levels in the RIRI group were increased,the renal function and tissue damage were more severe,the degree of cell apoptosis was aggravated,the MDA level was increased,and the SOD activity was decreased,the Nrf2 and HO-1 protein and mRNA levels were downregulated,the NOD-like receptor protein 3(NLRP3),Cle-Caspase-1(the activated form of Caspase-1)and gasdermin D(GSDMD)-N protein levels were upregulated,the NLRP3,Caspase-1 and GSDMD-N mRNA levels were increased,and the release of IL-1β and IL-18 was increased.Compared with the RIRI group,the BUN and Scr levels in rats after AS-Ⅳ treatment were decreased,the degree of renal function and tissue damage was reduced,the degree of cell apoptosis was decreased,the MDA level was decreased,and the SOD activity was increased,the Nrf2 and HO-1 protein and mRNA levels were increased,the NLRP3,Cle-Caspase-1 and GSDMD-N protein levels were decreased,the NLRP3,Caspase-1 and GSDMD-N mRNA levels were decreased,and the release of IL-1β and IL-18 was reduced.Compared with the RIRI+AS-Ⅳ(20 mg/kg)group,the MDA level and SOD activity in rats of the RIRI+AS-Ⅳ+Brusatol group were increased,the Nrf2 and HO-1 protein and mRNA levels were decreased,the NLRP3,Cle-Caspase-1 and GSDMD-N protein levels were upregulated,the NLRP3,Caspase-1 and GSDMD-N mRNA levels were increased,and the release of IL-1β and IL-18 was increased.Conclusions AS-Ⅳ may alleviate RIRI in rats by inhibiting oxidative stress response and pyroptosis,and this mechanism is related to the activation of Nrf2/HO-1 signaling pathway.关键词
细胞焦亡/肾缺血-再灌注损伤/肾移植/黄芪甲苷/核因子E2相关因子2/血红素加氧酶-1/肾功能损伤/NOD样受体蛋白3/氧化应激反应Key words
Cell pyroptosis/Renal ischemia-reperfusion injury/Kidney transplantation/Astragaloside Ⅳ/Nuclear factor E2-related factor 2/Heme oxygenase-1/Renal function damage/NOD-like receptor protein 3/Oxidative stress response分类
医药卫生引用本文复制引用
李晓凤,韩宇航,张笛,张国欣,张凌云..黄芪甲苷通过激活Nrf2/HO-1通路抑制NLRP3介导的焦亡缓解肾缺血-再灌注损伤[J].器官移植,2026,17(5):772-782,11.基金项目
甘肃省自然科学基金(23JRRA1718) （23JRRA1718）
