浓缩生长因子诱导髓源性抑制细胞募集和功能激活促进糖尿病足溃疡免疫稳态重建的机制研究OA

Objective:To explore the mechanism of concentrated growth factor(CGF)remodeling the immune homeostasis of diabetes foot ulcer(DFU)by inducing recruitment and functional activation of myeloid-derived suppressor cells(MDSCs),and to evaluate the impact of glycemic control on the efficacy of CGF,providing a new immune regulation strategy for clinical use.Methods:DFU model of C57BL/6 mice induced by streptozotocin(STZ)was established and randomly divided into CGF group(wound covered with autologous CGF gel),control group(PBS treatment),and CGF combined with glycemic intervention group(CGF+GI group,receiving daily subcutaneous insulin injection to maintain blood glucose at 8～12 mmol/L based on CGF treatment).Flow cytometry was used to detect proportion of MDSCs(CD11b⁺ Gr-1⁺)and expressions of functional molecules ARG-1/iNOS in the wound;immunohisto-chemistry/fluorescence analysis for tissue localization;ELISA quantification of inflammatory factors(IL-10,TGF-β1,TNF-α,IL-6);principal component analysis(PCA)integrated multidimensional immune indicators;mediation effect model verified pathway mecha-nism.Results:On the 7th day,proportion of MDSCs in CGF group reached its peak(P<0.001),and mean fluorescence intensity(MFI)of ARG-1 was significantly increased(P<0.001).Compared with CGF group,CGF+GI group exhibited a further increase in MDSCs proportion(P<0.05)and ARG-1 MFI(P<0.01)on day 7,along with higher levels of anti-inflammatory factors IL-10 and TGF-β1(P<0.05)and lower levels of pro-inflammatory factors TNF-α and IL-6(P<0.05).Anti-inflammatory factors IL-10 and TGF-β1 were significantly up-regulated,while pro-inflammatory factors TNF-α and IL-6 were significantly inhibited(both P<0.001).The median healing time in CGF group was shortened to 12.5 days(control group 18.7 days,P<0.001),and PCA confirmed that the"immunosup-pressive/repair axis"(contribution rate 46.37%)dominated steady-state reconstruction.The mediating effect showed that CGF accelerates healing through a chain pathway of"MDSCs recruitment → ARG-1/iNOS ↑→ anti-inflammatory factors ↑"(β=0.263).Conclusion:CGF continuously activates ARG-1/iNOS immunosuppressive function of MDSCs,synergistically regulates inflammatory factor net-work,reconstructs the immune homeostasis of DFU,significantly promotes wound healing,and glycemic control can further enhance the immunomodulatory effects of CGF,and provides a new strategy for DFU immune targeted therapy.