Effect of Yiqi Yangyin Huoxue Formula（益气养阴活血方）on Oxidative Stress and Inflammatory Injury in Membranous Nephropathy Model Rats：Based on the NOX4-mediated SDF-1α/CXCR4 Signaling Pathway
10.13288/j.11-2166/r.2026.13.013
- VernacularTitle:基于NOX4介导的SDF-1α/CXCR4信号通路探讨益气养阴活血方对膜性肾病模型大鼠氧化应激及炎症损伤的影响
- Author:
Xiaoxiao GUO
1
;
Chundong SONG
1
;
Hanhan ZHANG
1
;
Ke SONG
1
;
Chenchen CHEN
1
;
Haoran JIANG
1
;
Ying DING
1
Author Information
1. Department of Pediatrics，First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou，450003
- Publication Type:Journal Article
- Keywords:
membranous nephropathy;
oxidative stress;
inflammation;
nicotinamide adenine dinucleotide phosphate oxidase 4;
Stromal cell-derived factor-1α;
CXC chemokine receptor type 4;
podocytes;
Yiqi Yangyin Huoxue Formula （益气养阴活血方）
- From:
Journal of Traditional Chinese Medicine
2026;67(13):1431-1439
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the potential mechanism of Yiqi Yangyin Huoxue Formula （益气养阴活血方， YYHF） in the treatment of membranous nephropathy （MN） based on the NOX4-mediated stromal cell-derived factor-1α（SDF-1α）/CXC chemokine receptor 4 （CXCR4） signaling pathway. MethodsA total of 42 male SD rats were randomly divided into blank group （n=6） and modeling group （n=36）. The modeling rats were given a single injection of sheep antirat Fx1A （6 ml/kg） serum into the tail vein to establish MN model. Thirty-six rats with successful modeling were further divided into model group （normal saline， 10 ml/kg）， benazepril group （10 mg·kg-1·d-1）， the medium-dose YYHF group （11.0 g·kg-1·d-1） and high-dose YYHF group （22.0 g·kg-1·d-1）， with 9 rats in each group. All groups received daily intragastric administration for 6 consecutive weeks. During the experimental period， the general condition of rats in each group was observed. After gavage administration finished， a fully automated biochemical analyzer was used to measure the 24-hour urine total protein （24 h-UTP） and serum biochemical parameters， including albumin （ALB）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， serum creatinine （SCr）， total cholesterol （TC）， and triglyceride （TG）. Hematoxylin-eosin （HE） staining and periodic acid-silver metheramine （PASM） staining were used to observe the histopathological changes of renal tissues in each group of rats. The levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were detected by ELISA. The protein expression levels of NOX4， SDF-1α， CXCR4， Nrf2， nuclear factor kappa B subunit p65 （NF-κB p65） and podocyte slit diaphragm protein nephrin in rat renal tissues were detected by Western Blotting. The mRNA expressions of NOX4， SDF-1α， CXCR4， Nrf2， NF-κB p65 and Nephrin in renal tissues were detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultsCompared to the blank group， rats in the model group exhibited typical features of MN， including lethargy， reduced activity， dull and coarse fur， marked edema， and massive proteinuria. Compared to the model group， these abnormal conditions were improved to varying degrees in all treatment groups. The high-dose YYHF group showed a level of improvement comparable to that of the benazepril group， with overall recovery superior to that of the medium-dose YYHF group. Compared to the blank group， the model group showed increased levels of 24 h-UTP， BUN， SCr， TC and TG， decreased level of ALB， increased levels of MDA and protein and mRNA expressions of NOX4， SDF-1α， CXCR4 and NF-κB p65 in renal tissue， along with decreased levels of SOD and protein and mRNA expressions of Nrf2， Nephrin （P＜0.01）， accompanied by severe renal pathological damage. Compared to the model group， the benazepril and the medium- and high-dose YYHF groups showed significant improvements in the above indicators （P＜0.01）， along with alleviation of renal pathological injury. The 24 h-UTP level in the high-dose YYHF group was lower than that in the medium-dose group （P＜0.01）， while no statistically significant difference was observed among the other treatment groups （P＞0.01）. ConclusionYYHF may alleviate oxidative stress and inflammatory responses by down-regulating the expression of NOX4 and inhibiting the SDF-1α/CXCR4-Nrf2 signaling pathway， thereby improving podocyte damage and protecting renal function.
