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  

Study on the mechanism of FPS-ZM1 in AGE accumulation inhibition and wound healing promotion of diabetic foot ulcers

作　　者：张晶鑫 赵旭东 王剑涛 陈方泽 李雷 ZHANG Jingcin;ZHAO Xudong;WANG Jiantao(The First Clinical Medical College,Xuzhou Medical University,Xuzhou 221000,China)

机构地区：[1]徐州医科大学第一临床医学院,221000 [2]徐州医科大学附属医院全科医学科

出　　处：《中国糖尿病杂志》2025年第3期215-220,共6页Chinese Journal of Diabetes

基　　金：江苏省卫健委老年健康项目(LK2021015);江苏省大学生创新训练项目(202310313123Y);徐州市科技局项目(KC23275)。

摘　　要：目的 探讨AGE受体(RAGE)拮抗剂FPS-ZM1抑制AGE蓄积促进糖尿病足溃疡(DFU)大鼠创面修复的机制。方法 将30只SD大鼠分为正常对照(Con)组、假手术(Sham)组、DFU组、FPS-ZM1处理(DFU+FPS-ZM1)组、磷酸盐缓冲液处理(DFU+PBS)组,每组6只。Masson染色观察创面结构,ELISA检测血清和组织中AGE、TNF-α、基质金属蛋白酶9(MMP-9)、VEGF蛋白表达,Western blot法检测RAGE、VEGF受体(VEGFR)、CD31、核因子κB(NF-κB)蛋白表达。结果 与Con、Sham组比较,DFU组创面胶原纤维蓝染少,排列紊乱,分布稀疏。与DFU、DFU+PBS组比较,DFU+FPS-ZM1组创面肉芽组织中可见明显的胶原纤维蓝染,沉积层数较多,分布相对整齐有序。与Sham组比较,DFU组血清和组织中AGE、TNF-α、MMP-9蛋白表达及NF-κB、RAGE蛋白表达升高(P<0.05),血清和组织中VEGF蛋白表达及CD31、VEGFR蛋白表达降低(P<0.05)。与DFU组比较,DFU+FPS-ZM1组血清和组织中AGE、TNF-α、MMP-9蛋白表达及NF-κB、RAGE蛋白表达降低(P<0.05),血清和组织中VEGF蛋白表达及CD31、VEGFR蛋白表达升高(P<0.05)。与DFU+FPS-ZM1组比较,DFU+PBS组血清和组织中AGE、TNF-α、MMP-9蛋白表达及NF-κB、RAGE蛋白表达升高(P<0.05),血清组织中VEGF蛋白及CD31、VEGFR蛋白表达降低(P<0.05)。结论 RAGE拮抗剂FPS-ZM1通过抑制NF-κB炎症信号通路,下调MMP-9并上调VEGF,促进DFU创面愈合。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 kB(NF-kB)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-ZMI1 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-αand MMP-9 proteins,NF-kB 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-αand MMP-9 proteins,NF-kB 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-αand MMP-9 proteins,NF-kB 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-ZMI down-regulates MMP-9 and up-regulates VEGF by inhibiting the NF-kB inflammatory signaling pathway,and promotes DFU wound healing.

关 键 词：糖尿病足溃疡 糖基化终产物 基质金属蛋白酶9 血管内皮生长因子 内皮祖细胞 

分 类 号：R587.2[医药卫生—内分泌]