Neferine alleviates inflammation in rats with chronic skin ulcer by regulating AMPK/mTOR/NLRP3 signaling pathway
Objective:To investigate the effect of neferine(Nef)on inflammatory response in rats with chronic skin ulcer(CSU)by regulating AMP activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway.Methods:90 rats were randomly divided into blank control group(NC group),CSU group,Nef group,AMPK inhibitor(Compound C)group,and Nef +Compound C group,with 18 rats in each group.Except the blank control group,rats in the other groups were injected with hydrocortisone and sprayed with Staphylococcus aureus to establish CSU rat model.After the modeling was completed,20%Nef and10 μmol·L-1 Compound C were added to20%hypertonic saline gel in the Nef group and Compound C group,respectively,and then applied to the wound.In the Nef + Compound C group,20%Nef and 10 μmol·L-1 Compound C were added to 20%hypertonic saline gel and then applied to the wound.In the NC group and the CSU group,the same amount of saline gel was applied to the wound.All groups were treated for 2 weeks.The healing of skin wound in rats was observed.The levels of IL-1β,IL-8 and TNF-α in serum were detected by ELISA.The level of HyP in wound granulation tissue was detected by hydrolysis method.HE staining was used to detect pathological changes of granulation tissue.And the expression levels of CCL4,CCL2,CXCL12 and AMPK/mTOR/NLRP3 signaling pathway proteins were detected by Western blotting.Results:New granulation tissue and inflammatory cell infiltration were observed in the CSU group,the contents of IL-1β,IL-8 and TNF-α in CSU group were obviously higher than those in the NC group(P＜0.05).Compared with the CSU group,the wound healing rate,content of HyP,and level of p-AMPK/AMPK protein in Nef group were obviously higher(P＜0.05),the contents of IL-1β,IL-8,TNF-α,and the levels of CCL2,CXCL12,CCL4,mTOR,and NLRP3 proteins were obviously lower(P＜0.05),while the trend in Compound C group was the opposite(P＜0.05).Compound C eliminated the reducing effect of Nef on inflammatory reaction of CSU rats.Conclusion:Nef may reduce the inflammatory response of CSU rats by regulating AMPK/mTOR/NLRP3 signaling pathway.
neferineAMPK/mTOR/NLRP3 signal pathwaychronic skin ulcerinflammatory reactionrats
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NSTL
万方数据
维普
