Study on the mechanism of FPS-ZM1 in AGE accumulation inhibition and wound healing promotion of diabetic foot ulcers
10.3969/j.issn.1006-6187.2025.03.011
- VernacularTitle:FPS-ZM1抑制糖基化终产物蓄积促进糖尿病足溃疡创面愈合机制的研究
- Author:
Jingxin ZHANG
1
;
Xudong ZHAO
;
Jiantao WANG
;
Fangze CHEN
;
Lei LI
Author Information
1. 221000 徐州医科大学第一临床医学院
- Publication Type:Journal Article
- Keywords:
Diabetic foot ulcer;
AGE;
MMP-9;
VEGF;
Endothelial progenitor cell
- From:
Chinese Journal of Diabetes
2025;33(3):215-220
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism by which AGE receptor(RAGE)antagonist FPS-ZM1 inhibits AGE accumulation and promotes wound repair in rats with diabetic foot ulcer(DFU).Methods A total of 30 SD rats were divided into normal control(Con)group,sham operation group(Sham),DFU group,FPS-ZM1 treatment group(DFU+FPS-ZM1),and phosphate buffer saline treatment group(DFU+PBS),with 6 rats in each group.Masson staining was used to evaluate the wound surface structure.ELISA was used to detect the expression of AGE,TNF-α,matrix metalloproteinase 9(MMP-9),and VEGF proteins in serum and tissues,and Western blot method was used to test the expression of RAGE,VEGF receptor(VEGFR),CD31,and nuclear factor κB(NF-κB)proteins.Results Compared with the Con and Sham groups,the collagen fibers had less indigo staining,disordered arrangement and sparse distribution in DFU group.Compared with the DFU and DFU+PBS groups,the DFU+FPS-ZM1 group showed obvious blue staining of collagen fibers in the wound granulation tissue,and the number of deposition layers was relatively neat and orderly.Compared with Sham group,the expressions of AGE,TNF-α and MMP-9 proteins,NF-κB and RAGE proteins in serum and tissues were increased(P<0.05),and the expressions of VEGF protein and CD31 and VEGFR proteins in serum and tissues were decreased in DFU group(P<0.05).Compared with DFU group,the expressions of AGE,TNF-α and MMP-9 proteins,NF-κB and RAGE proteins in serum and tissues decreased(P<0.05),and the expression of VEGF protein and CD31 and VEGFR proteins in serum and tissues increased in DFU+FPS-ZM1 group(P<0.05).Compared with DFU+FPS-ZM1 group,the expressions of AGE,TNF-α and MMP-9 proteins,NF-κB and RAGE proteins in serum and tissues increased(P<0.05),and the expressions of VEGF protein,CD31 and VEGFR proteins in serum tissues decreased in DFU+PBS group(P<0.05).Conclusions The RAGE antagonist FPS-ZM1 down-regulates MMP-9 and up-regulates VEGF by inhibiting the NF-κB inflammatory signaling pathway,and promotes DFU wound healing.
