Shen-Xiankang formula alleviates renal fibrosis in chronic kidney disease mice by regulating Smad3-mediated ferroptosis
10.3969/j.issn.1000-4718.2024.06.016
- VernacularTitle:肾纤康通过调节Smad3介导的铁死亡缓解CKD小鼠肾纤维化
- Author:
Yufang NI
1
;
Luna ZHANG
;
Qiong ZHANG
;
Li WANG
;
Jianchun LI
Author Information
1. 西南医科大学附属中医医院中西医结合研究中心,四川 泸州 646000
- Keywords:
Shen-Xiankang formula;
chronic kidney disease;
ferroptosis;
Smad3 protein;
activating tran-scription factor 3
- From:
Chinese Journal of Pathophysiology
2024;40(6):1097-1104
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To evaluate the therapeutic effect of Shen-Xiankang formula on renal interstitial fibrosis in-duced by unilateral ureteral obstruction(UUO)in mice and to elucidate its underlying mechanisms.METHODS:Thirty-two C57BL/6 mice were randomly divided into sham group,UUO model group,and Shen-Xiankang formula intervention groups receiving either a low dose(150 mg·kg-1·d-1)or a high dose(450 mg·kg-1·d-1),with 8 mice in each group.All mice except those in sham group underwent UUO to establish chronic kidney disease(CKD)model.After modeling,cor-responding doses of Shen-Xiankang or an equivalent volume of saline were administered daily for 7 d.Upon completion of treatment,renal tissues were collected for hematoxylin-eosin(HE)and Masson staining to assess tissue damage and fibro-sis.Immunohistochemistry and Western blot analyses were used to detect the markers of fibrosis,oxidative stress,and fer-roptosis.The effect of Shen-Xiankang formula on the interaction between activating transcription factor 3(ATF3)and Smad3 was assessed using co-immunoprecipitation(Co-IP).RESULTS:The untreated UUO model group exhibited nota-ble pathological changes such as expanded renal tubules and collagen deposition.Shen-Xiankang treatment significantly alleviated these changes(P<0.05).It markedly reduced Smad3 phosphorylation,ATF3,4-hydroxynonenal(4-HNE),and NADPH oxidase 4(NOX4)aberrant expression,while increasing glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)expression.Co-IP results indicated a significant modulation of the ATF3-Smad3 interac-tion by Shen-Xiankang.CONCLUSION:Shen-Xiankang formula effectively mitigates UUO-induced renal interstitial fi-brosis in mice.The mechanism may involve modulating the ATF3/Smad3 interaction,which in turn attenuates oxidative stress and ferroptosis,consequently leading to the amelioration of renal fibrosis.These findings provide important insights for further research and clinical application of Shen-Xiankang formula.
