Effects and mechanism of astilbin on renal injury in chronic renal failure rats
10.6039/j.issn.1001-0408.2025.04.08
- VernacularTitle:落新妇苷对慢性肾功能衰竭大鼠肾损伤的影响及机制
- Author:
Xiaowei GAO
1
;
Yingying LIU
;
Cong HAN
;
Shifei HAO
Author Information
1. 山东中医药大学附属医院急诊科,济南 250011
- Publication Type:Journal Article
- Keywords:
astilbin;
chronic renal failure;
renal injury;
renal fibrosis;
Jagged-1/Notch-1 signaling pathway
- From:
China Pharmacy
2025;36(4):434-439
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effect and potential mechanism of astilbin(AST)on renal injury in chronic renal failure(CRF)rats based on the Jagged-1/Notch-1 signaling pathway.METHODS CRF model was constructed by 5/6 nephrotomy.The successfully modeled rats were randomly separated into Model group,AST low-dose group(AST-L group),AST high-dose group(AST-H group),high-dose of AST+Notch pathway activator(Jagged-1/FC chimerin,referred to as"JFC")group(AST-H+JFC group),and control group(CK group)for open surgery without resection was set up,with 10 rats in each group.The rats in the AST-L group and AST-H group were given 40 and 80 mg/kg AST,respectively;the rats in the AST-H+JFC group were simultaneously given 80 mg/kg AST and 0.5 mg/kg JFC,and the rats in the CK group and Model group were given an equal volume of normal saline,once a day,for 4 weeks.After the last administration,the serum levels of blood urea nitrogen(BUN),serum creatinine(SCr),and the level of 24 h urinary protein(UP)in urine,as well as the serum levels of lactate dehydrogenase(LDH),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-10 in each group were detected.The morphology and fibrosis of renal tissue were observed.The content of adenosine triphosphate(ATP)and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were detected.The protein expressions of transforming growth factor-β(TGF-β),hypoxia-inducible factor-1α(HIF-1α),α-smooth muscle actin(α-SMA),cleaved-caspase-3,Jagged-1 and Notch-1 in renal tissue were also observed.RESULTS Compared with CK group,the renal tissue of rats in the Model group was obviously damaged,renal tissue fibrosis was severe;the serum BUN and SCr levels,urine UP level,serum LDH,TNF-α and IL-6 levels,as well as the protein expressions of TGF-β,HIF-1α,α-SMA,cleaved-caspase-3,Jagged-1 and Notch-1 in renal tissue were significantly increased,while the serum IL-10 level,ATP content and activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were significantly decreased(P＜0.05).Compared with Model group,the renal tissue damage and fibrosis in the AST groups were reduced,the serum BUN and SCr levels,urine UP level,serum LDH,TNF-α and IL-6 levels,and the protein expressions of TGF-β,HIF-1α,α-SMA,cleaved-caspase-3,Jagged-1 and Notch-1 were significantly decreased,while the serum IL-10 level,ATP content and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria were significantly increased;the changes in the aforementioned indicators in AST-H group were more significant than those in the AST-L group(P＜0.05).JFC could significantly reverse the improvement effect of high dose of AST on renal injury in CRF rats(P＜0.05).CONCLUSIONS AST can reduce inflammation in CRF rats,alleviate renal tissue damage and fibrosis,and improve renal mitochondrial capacity metabolism,possibly by inhibiting the Jagged-1/Notch-1 signaling pathway.
