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
10.3870/j.issn.1004-0781.2025.06.002
- VernacularTitle: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
- Author:
Hong FANG
1
;
Chundong SONG
;
Shoulin ZHANG
;
Xu WANG
;
Yanmin FAN
;
Hanshu JI
;
Jichang BU
;
Ke SONG
;
Chenchen CHEN
;
Ying DING
Author Information
1. 河南中医药大学第一附属医院儿科医院,郑州 450099;河南中医药大学儿科医学院,郑州 450046
- Publication Type:Journal Article
- Keywords:
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
- From:
Herald of Medicine
2025;44(6):847-853
- CountryChina
- Language:Chinese
-
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.