6-Gingerol promoting the oral mucosal healing in rats based on PKB/KIF14 signaling pathway
Objective To explore the promoting effect of 6-gingerol extract on mucosal healing in experimental oral ulcer rats and the regulation of protein kinase B(PKB)/driver protein family member 14(KIF14)signaling pathway.Methods Fifty rats were ran-domly divided into normal group,model group,6-gingerol group,LY294002 group and LY294002 combined with 6-gingerol group.Except for the normal group,the other groups were used to establish oral ulcer model by glacial acetic acid cauterization.Rats in the 6-gingerol group were injected with 6-gingerol 6 mg·kg-1,rats in the LY294002 group were injected with LY294002 0.3 mg·kg-1,rats in the LY294002 combined with 6-gingerol group were injected with LY294002 0.3 mg·kg-1,and rats in the 6-gingerol combined with 6-gingerol group were injected with LY294002 0.3 mg·kg-1 for 30 minutes,then tail vein injection of 6-gingerol 6 mg·kg-1,once a day,for 7 consecutive days.The ulcer area was calculated,the pathological changes were observed by HE staining,the inter-leukin 6(IL-6),interleukin 1β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by enzyme linked immunosorbent assay(ELISA),and the matrix metalloproteinase 2(MMP-2)and MMP-9 were detected by quantitative real-time polymerase chain reac-tion(qRT-PCR).The relative expression levels of phosphatidylinositol 3 kinase(PI3K),PKB and KIF14 proteins were detected by Western blotting.Results In the model group,a large number of inflammatory cells infiltrated the mucosa and the epithelial cells were necrotic and shed,and no new fibrocytes were formed.In 6-gingerol group,mucosal epithelium was covered and ulcer tended to heal.In LY294002 group,a large number of inflammatory cells were infiltrated,the epithelial structure was destroyed,and the mucosal epithelial cells were shed and necrotic.The inflammatory cell infiltration in LY294002 combined with 6-gingerol group was reduced,and the pathological changes were reduced in 6-gingerol group.Compared with model group,the ulcer area in 6-gingerol group was decreased,the levels of IL-6,TNF-α and IL-1β,the relative expression levels of MMP-2 and MMP-9 mRNA decreased,the relative expression levels of p-PI3K,p-PKB and KIF14 increased,and the ulcer area in LY294002 group increased.The levels of IL-6,TNF-α and IL-1β were increased,the relative expression levels of MMP-2 and MMP-9 mRNA increased,and the relative ex-pression levels of p-PI3K,p-PKB and KIF14 decreased(P<0.05).Compared with LY294002 combined with 6-gingerol group,the ulcer area of 6-gingerol group was decreased,the levels of IL-6,TNF-α and IL-1β,the relative expression levels of MMP-2 and MMP-9 mRNA decreased,the relative expression levels of p-PI3K,p-PKB and KIF14 increased,and the ulcer area of LY294002 group increased.The levels of IL-6,TNF-α and IL-1β were increased,the relative expression levels of MMP-2 and MMP-9 mRNA increased,and the relative expression levels of p-PI3K,p-PKB and KIF14 decreased(P<0.05).Conclusion 6-Gingerol,a ginger extract,can promote wound healing in rats with oral ulcer,possibly through activating PKB/KIF14 signaling pathway.