Exploring the Action Mechanism of Yiqi Yangyin Huoxue Formula Improving Renal Injury in Rats with Diabetic Nephropathy Based on Endoplasmic Reticulum Stress-triggered Ferroptosis
10.3870/j.issn.1672-0741.24.10.005
- VernacularTitle:基于内质网应激触发铁死亡探讨益气养阴活血方改善糖尿病肾病大鼠肾损伤的作用机制
- Author:
Hong FANG
1
;
Chundong SONG
1
;
Xu WANG
1
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:
Yiqi Yangyin Huoxue Formula;
diabetic nephropathy;
endoplasmic reticulum stress;
ferroptosis;
XBP1/HRD1 signaling pathway
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(2):172-179
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of improving renal injury in rats with diabetic nephropathy(DN)by Yiqi Yangyin Huoxue Formula.Methods Male SD rats were fed with high-fat and high-sugar diet,combining with a single in-traperitoneal injection of streptozotocin to establish DN model.The rats were divided into the model group,the valsartan group,the equal-dose group of Yiqi Yangyin Huoxue Formula(equal-Yi group),and the high-dose group of Yiqi Yangyin Huoxue For-mula(high-Yi group)according to the method of randomized numerical table.The treatment groups were administered by gavage from the tenth week of the modeling period.Levels of 24-hour urinary total protein(UTP),blood urea nitrogen(BUN),serum creatinine(SCr),glucose(GLU),cholesterol(CHOL),and triglycerides(TG)were measured.Serum malondialdehyde(MDA)lev-els were detected by ELISA.Western blot was used to detect the protein expression of XBP1,HRD1,Nrf2,SLC7A11,and GPX4 in rat kidney tissues.The qRT-PCR was used to detect the mRNA expression levels of XBP1,HRD1,Nrf2,SLC7A11,and GPX4 in rat kidney tissues.HE staining was used to observe the pathological changes in the kidney tissues of rats in each group.Results Compared with the blank group,rats in the model group showed significantly higher levels of 24h-UTP,BUN,SCr,GLU,CHOL,and TG(all P<0.01),significantly higher levels of serum MDA(P<0.01),significantly higher expression of XBP1,HRD1 protein and mRNA in renal tissues(all P<0.01),significantly lower protein and mRNA expression of Nrf2,SLC7A11,and GPX4(all P<0.01),and renal pathological damage was severe.Compared with the model group,24h-UTP,BUN,SCr,GLU,CHOL,TG levels were significantly reduced in the valsartan group,equal-Yi group and high-Yi group(all P<0.01),serum MDA levels were significantly reduced(P<0.01),XBP1,HRD1 protein and mRNA expressions in renal tissues were significantly reduced(all P<0.01),Nrf2,SLC7A11,GPX4 protein and mRNA expression were significantly increased(all P<0.01),and renal pathology was improved.Conclusion Yiqi Yangyin Huoxue Formula may inhibit the occurrence of endo-plasmic reticulum stress,attenuate iron death injury,protect renal function and ameliorate renal injury by regulating XBP1/HRD1/Nrf2 signaling pathway.