温阳生肌膏通过p38MAPK/NF-κB信号通路减轻糖尿病创面炎症反应的研究OA

Objective To explore the mechanism underlying the regulation of the p38 MAPK/NF-κB signaling pathway by Wenyang Shengji Ointment(温阳生肌膏,WYSGO)in ameliorating inflammation in high glucose-induced macrophage-fibroblast cocultures.Methods Models of high glucose-treated RAW264.7,NIH3T3,and their co-culture system were established.The cells were divided into normal,model,and WYSGO groups.Cell proliferation,migration,macrophage polarization,TNF-α content,and related protein expression were assessed by CCK-8 assay,scratch wound healing assay,flow cytometry,ELISA,and Western blotting(WB),respec-tively.Results Compared with the model group,WYSGO significantly promoted cell proliferation(P<0.01 or P<0.001),inhibited M1 polarization of RAW264.7 cells(P<0.001),and promoted their M2 polarization(P<0.001).In addition,WYSGO restored the migra-tion ability of NIH3T3 and co-cultured cells(P<0.01),downregulated the expression of p38 MAPK and NF-κB p65 proteins in NIH3T3 cells(P<0.05),and significantly reduced the levels of p38 MAPK,NF-κB p65,and phosphorylated NF-κB p65(p-NF-κB p65)proteins in RAW264.7 and co-cultured cells(P<0.05,P<0.01,or P<0.001),as well as the level of the inflammatory factor TNF-α(P<0.001).Conclusion Fibroblast dysfunction is alleviated by WYSGO through the suppression of the p38 MAPK/NF-κB path-way activation,which subsequently reverses macrophage M1 polarization,reduces TNF-α release,and blocks the transmission of inflammatory signals in macrophage-fibroblast interactions.