MEBT/MEBO In The Regeneration Of Chronic Refractory Wound Influence Of The NRF2/HO-1/NQO1 Axis

Objective: To investigate the mechanism of skin regeneration therapy(MEBT/MEBO)in promoting the regeneration and repair of chronic refractory wounds in rats through oxidative stress related signaling pathway NRF2/HO-1/NQO1 axis.Methods: 90 SPF Wistar rats were randomly divided into blank group and the control group(acute skin defect),chronic wound group(model group,MEBO group,rb-b FGF group),a total of 5 groups,18 / group,model group,MEBO group,rb-b FGF group build at the same time of chronic wound model.(1)The wound healing rate of each group was detected on the3 rd,7th and 14 th day of modeling.(2)Wound tissues were collected,and morphological changes of cells,granulation,blood vessels and collagen fibers were examined by HE staining and Masson staining.(3)Concentration of Malondialdehyde(MDA)and activity of SOD(Manganese superoxide dismutase)in tissues were measured by colorimetry;(4)The average optical density of HO-1 and NQO1 in each group was determined by immunohistochemistry.(5)The expression of NRF2 protein in tissues was determined by immunofluorescence method.(6)The protein expression levels of HO-1 and NQO1 in tissues were determined by Western-blo method.(7)The transcription levels of HO-1 and NQO1 m RNA in tissues were determined by Real-time PCR detection.Results:(1)to 5 groups of rats to intervene treatment for 14 days,MEBO group and rb-b FGF group rat wound healing rate is better than that of model group(P< 0.05);(2)After7 and 14 days of intervention,neovascularization,collagen fibers and fibroblasts in MEBO and rb-b FGF groups were more and more better than those in model group(P < 0.05);(3)After 3,7 and 14 days of intervention,MDA content in wound tissues of the five groups was better than that of the model group except rb-b FGF group on the third day(P<0.05);SOD activity in MEBO group was better than that in model group(P<0.05);(4)After 3,7 and 14 days of intervention treatment,the mean optical density values of HO-1 and NQO1 in MEBO group and rb-b FGF group were higher than those in model group(P<0.05);(5)After 3,7 and14 days of intervention,NRF2 protein expression in MEBO group and rb-b FGF group was better than that in model group(P<0.05);(6)After 3,7 and 14 days of intervention,the protein expression levels of HO-1 and NQO1 in MEBO group and rb-b FGF group were better than those in model group(P < 0.05);(7)After 3,7 and 14 days of intervention,m RNA transcription levels of HO-1 and NQO1 in MEBO group and rb-b FGF group were better than those in model group(P<0.05).Conclusion: MEBT/MEBO may reduce oxidative damage and promote regeneration through activation of NRF2/HO-1/NQO1 axis.