基于Nrf2/SLC7 A11/Gpx4通路研究当归芍药散对肾病综合征幼鼠干预作用OA
Study on the Intervention of Danggui Shaoyao Powder on Oxidative Stress Injury of Kidneys in Juvenile Rats With Nephrotic Syndrome Based on the Nrf2/SLC7A11/Gpx4 pathway
目的:探讨当归芍药散对肾病综合征(PNS)幼鼠肾脏核因子 E2 相关因子(Nrf2)/溶质载体家族7 A11(SLC7A11)/谷胱甘肽过氧化物酶4(Gpx4)通路及氧化应激损伤干预作用.方法:4 周龄 SD 幼鼠随机分为6 组,即空白组(CON 组)、模型组(MOD 组)、坎地沙坦组(KDS 组)、当归芍药散组(DSS 组)、联合组(COM 组)、阻断剂组(ANT 组),除 CON 组外,各组首先以阿霉素分次尾静脉注射建立肾病综合征模型,造模后各组分别以相应药物干预,联合组予以当归芍药散联合坎地沙坦方案,药物干预持续4 周.第4 周末以考马斯亮蓝法检测幼鼠 24 h 尿蛋白定量(24 h UTP)、生化法检测幼鼠血清白蛋白(ALB)、尿素氮(BUN)、肌酐(CREA),并以 ELISA 法检测幼鼠肾组织活性氧(ROS)、超氧化物歧化酶(SOD)、丙二醛(MDA),免疫荧光法检测谷胱甘肽过氧化物酶(GPx)、8-羟基脱氧鸟苷(8-OHdG)、亚铁离子(Fe2+)水平.采用 Western blot 法检测幼鼠肾脏 Nrf2/SLC7A11/Gpx4 通路相关因子.结果:干预4 周后,与 CON 组比较,MOD 组生化指标 24 h UTP 水平升高,ALB 水平下降,氧化应激指标 ROS、MDA、8-OHdG、Fe2+水平升高,SOD、GSH 水平下降,Nrf2、SLC7A11、Gpx4 呈低表达,差异均有统计学意义(P<0.05),与 MOD 组比较,药物干预组即 KDS 组、DSS 组、COM 组,上述指标均有所改善,差异有统计学意义(P<0.05),COM 组与 DSS 组、KDS 组对比,改善更加明显,差异有统计学意义(P<0.05),阻断剂 ML385 干预后,ANT 组的改善作用大幅降低,与 DSS 组对比差异有统计学意义(P<0.05).各组BUN、CREA 未见明显变化(P>0.05).结论:当归芍药散可调节肾病综合征幼鼠肾脏 Nrf2/SLC7A11/Gpx4 通路,缓解氧化应激损伤,对其肾脏具有保护作用.
Objective:To explore the intervention effect of Danggui Shaoyao Powder on the Nrf2/SLC7A11/Gpx4 pathway and oxidative stress injury in the kidneys of juvenile rats with nephrotic syndrome(PNS).Methods:4-week-old SD rats were randomly divided into six groups:CON group,MOD group,KDS group,DSS group,COM group and ANT group.Except for the CON group,in each group,the nephrotic syndrome model was established by intravenous injection of doxorubicin at regular intervals through the tail vein.After modeling,each group was intervened with the corresponding drug.The combined group was given the Danggui Shaoyao Powder combined with candesartan regimen.The drug intervention lasted for 4 weeks.At the 4th week,the 24-hour urine protein quantification(24 hUTP)of the rats was detected by the Coomassie brilliant blue method,the serum albumin(ALB),blood urea nitrogen(BUN),and creatinine(CREA)of the rats were detected by the biochemical method,and the reactive oxygen species(ROS),superoxide dismutase(SOD),and malondialdehyde(MDA)in the renal tissue of the rats were detected by ELISA,and the levels of glutathione peroxidase(GPx),8-hydroxydeoxyguanosine(8-OHdG),and iron ions(Fe2+)were detected by immunofluorescence.The related factors of the Nrf2/SLC7A11/Gpx4 pathway in the kidneys of the rats were detected by Western blot method.Results:After 4 weeks of intervention,compared with the CON group,the 24 h UTP level was increased and the ALB level was decreased in the MOD group;the levels of ROS,MDA,8-OHdG and Fe2+of oxidative stress indicators were elevated,while SOD and GSH levels declined,and the expressions of Nrf2,SLC7A11 and Gpx4 were significantly downregulated,with statistically significant differences(P<0.05).Compared with the MOD group,all above indexes were markedly improved in KDS,DSS and COM groups(P<0.05).The improvement in the COM group was superior to that in DSS and KDS groups(P<0.05).After intervention with the blocker ML385,the protective efficacy of Danggui Shaoyao Powder was obviously abolished in the ANT group,and there was significant difference compared with the DSS group(P<0.05).No obvious changes of BUN and CREA were observed among all groups(P>0.05).Conclusion:Danggui Shaoyao Powder can regulate the Nrf2/SLC7A11/Gpx4 pathway in the kidneys of juvenile rats with nephrotic syndrome,alleviate oxidative stress damage,and exert a protective effect on their kidneys.
秦曼;张天照
黑龙江省中医药科学院 黑龙江省中医医院,黑龙江 哈尔滨 150036黑龙江省中医药科学院 黑龙江省中医医院,黑龙江 哈尔滨 150036
医药卫生
当归芍药散氧化应激肾病综合征幼鼠Nrf2/SLC7A11/Gpx4通路
Danggui Shaoyao PowderOxidative stressNephrotic syndromeJuvenile ratsNrf2/SLC7A11/Gpx4 pathway
《中医药学报》 2026 (9)
27-33,7
黑龙江省自然科学基金项目(PL2024H249)黑龙江省中医药管理局中医药科研项目(ZHY2025-091)
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