医药导报2025，Vol.44Issue(6)：847-853,7.DOI:10.3870/j.issn.1004-0781.2025.06.002
雷公藤多苷调节SIRT1/Nrf2/HO-1通路改善IgA肾病大鼠肾损伤的机制
Mechanism of Multi-Glycosides of Tripterygium Wilfordii in Improving Kidney Injury in IgA Nephropathy Model Rats Via the SIRT 1/Nrf 2/HO-1 Pathway
摘要
Abstract
Objective To explore the mechanism of IgA nephropathy(IgAN)caused by multi-glycosides of Tripterygium wilfordii(GTW)through the regulation of Silent information regulatory factor 1(SIRT 1)/nuclear transcription factor E2-related factor 2(Nrf 2)/antioxidant enzyme heme oxygenase 1(HO-1)signaling pathway.Methods Forty-five male SD rats were selected and randomly divided into two groups:the blank group(n=9)and the model group(n=36).In addition to the blank group,the BSA+CCl4+LPS group was used.At the end of 12 weeks,two rats were randomly selected for verification,and the model was successfully established.The 34 model rats were randomly divided into 3 groups:the model group(n=10),prednisone group(n=12),and GTW group(n=12).Urine,blood and kidney tissues were harvested 4 weeks after drug administration.Urinary erythrocyte number,24-h urinary protein quantification(24 h-UTP),alanine transaminase(ALT),serum albumin(ALB),urea nitrogen(BUN),and blood creatinine(SCr)were performed for each group;the protein expression of SIRT1,Nrf2,HO-1 and PINK1 was detected by Western blotting analysis;real-time polymerase chain reaction(RT-PCR)detection of SIRT1,Nrf2,HO-1 and PINK1 mRNA expression in rat kidney tissue;and detection of IgA deposition in the renal mesangial area by immunofluorescence.Kidney histopathological changes were observed in all the rats by hematoxylin-eosin(HE)staining.Results The results compared with those in the blank group,the urinary red blood cell count and 24 h-UTP,ALT,BUN,and SCr levels were significantly greater(P<0.01);The ALB level was significantly lower(P<0.01);renal tissue SIRT1,Nrf2,HO-1,PINK1 protein and mRNA expression were significantly lower(P<0.01);IgA deposition in the mesentery was obvious;renal pathological damage was severe;and the difference was statistically significant. Compared with those in the model group,urinary red blood cell counts and 24 h-UTP,ALT,BUN,and SCr levels in the prednisone and GTW groups were significantly lower (P<0.01);ALB levels were significantly greater (P<0.01);SIRT1,Nrf2,HO-1,PINK1 protein and mRNA expression were significantly greater (P<0.01);IgA deposition in the mesangial area was reduced,and renal pathology was improved,with statistically significant difference. Conclusions GTW may alleviate oxidative stress injury,protect renal function,and improve renal injury by activating the SIRT 1/Nrf 2/HO-1 signaling pathway.关键词
雷公藤多苷/IgA肾病/沉默信息调节因子1/核转录因子E2相关因子2/血红素氧合酶1/氧化应激Key words
Multi-glycosides of Tripterygium wilfordii/Immunoglobulin A nephropathy/Silent information regulatory factor 1/Nuclear transcription factor E2-related factor 2/Heme oxygenase 1/Oxidative stress分类
医药卫生引用本文复制引用
方虹,丁樱,宋纯东,张守琳,王旭,樊艳敏,季晗舒,卜继常,宋珂,陈晨晨..雷公藤多苷调节SIRT1/Nrf2/HO-1通路改善IgA肾病大鼠肾损伤的机制[J].医药导报,2025,44(6):847-853,7.基金项目
国家自然科学基金资助项目(82074493) （82074493）
河南省卫健委国家中医临床研究基地科研专项(2022JDZX003) （2022JDZX003）
河南省中医药科学研究重大专项(2023ZYZD02) （2023ZYZD02）
河南省中医药学科领军人才项目(豫卫中医函(2021)8号) （豫卫中医函(2021）
河南省"双一流"创建工程(HSRP-DFCTCM-2023-3-07). （HSRP-DFCTCM-2023-3-07）
