Mechanism of phenytoin sodium promoting wound healing in diabetic rats based on M1 macrophage inflammatory state
ZHANG Wenlong
LU Meiqi
WANG Xinglei
JIAO Ya
QI Yongjun
JIANG Duyin
Abstract：Objective To explore the promoting effect of phenytoin sodium(PHT)on chronic wound healing in dia-betic rats and its mechanism.Methods Six SD rats were randomly divided into the model group and the PHT treatment group,with three rats in each group.All rats were given a high-fat diet for 4 consecutive weeks and intraperitoneally inject-ed with streptozotocin(STZ)at 50 mg/kg for 3 consecutive days to establish the diabetic models.In the model group,200 μL of normal saline was injected into multiple sites at the wound edge on the back,while in the PHT treatment group,200 μL of PHT solution at 12.5 mg/mL was injected into multiple sites at the wound edge.Injections were given once every other day for a total of 10 times.The wound closure rate(WCR)was compared between groups on day 7,14,and 21 after intervention.RAW264.7 macrophages in the logarithmic growth phase were divided into the control group,model group,and PHT group.The model and PHT groups were treated with interferon-γ(IFN-γ)at 20 ng/mL and lipopolysaccharide(LPS)at 100 ng/mL to induce M1 polarization of macrophages.After 24 h,the PHT group was treated with PHT at 9 μmol/L.Flow cytometry was used to detect the proportion of CD86⁺ cells.Quantitative real-time polymerase chain reac-tion was used to detect the mRNA expression of inducible nitric oxide synthase(iNOS),arginase-1(ARG1),and interleu-kin-6(IL-6).Results On day 14 and 21 after intervention,the WCR in the PHT treatment group was higher than that in the model group(both P<0.05).Compared with the control group,the proportion of CD86⁺ cells in the model group was higher(P<0.05).Compared with the model group,the proportion of CD86⁺ cells in the PHT group was lower(P<0.05).Compared with the control group,the relative expression levels of iNOS and IL-6 in the model group were higher,while the relative expression level of ARG1 was lower(all P<0.05).Compared with the model group,the relative expression levels of iNOS and IL-6 in the PHT group were lower,while the relative expression level of ARG1 was higher(all P<0.05).Conclusion PHT can promote chronic wound healing in diabetic rats,and its mechanism may be related to inhibiting macrophage M1 polarization and promoting their transformation into an inflammation-repair state.
Keywords：diabetes mellituschronic woundphenytoin sodiumM1 macrophageinflammationwound heal-ingratsmechanism
Publication Date：2025-08-25
Online Publishing Date：2025-09-10(First online date of this platform, not the publication date of the document)
Pages：4( 48-51 )