Chronic Psychological Stress Induce Oxidative Stress Damage In Skin And Delay Anagen Of Hair Follicle

Purpose:1. Establish chronic restraint stress (CRS) model to observe the influenceof psychological stress on the hair follicle cycle of mice.2.Investigate the effect ofsubstance P, oxidative stress and mast cells on the alterations of hair follicle cycleinduced by psychological stress. Investigate the pathogenesis of hair loss, provide newideas and more reliable experimental basis for disease prevention, treatment and newdrug development.Methods:1. Establish CRS model with C57BL/6male mice, compared withcontrol mice and then, observe megascopic and morphological changes of animal hairfollicle cycle.2. Added two groups of intraperitoneal injection antioxidant or SPreceptor antagonist, all animals were assigned to the following four groups randomly:control, CRS, CRS+antioxidant (Tempol), CRS+SP receptor antagonist (RP67580).Anagen of mice dorsal hair follicles was induced by depilation, then skin specimenswere harvested on the day9and day19after depilation. Observed the alterations ofweigh, behavior, color of skin, morphology of hair follicle and score hair follicles.Determined corticosterone levels in plasma, thiobarbituric acid reactive substances(TBARS) levels, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)activity in skin. Counted ratio of degranulated mast cells by Toluidine blue staining.Counted SP+nerve fibers by immunofluorescence.Results:1. On the ninth day after depilation, compared with control mice, CRSmice skin appears pink, skin grayscale ratio was significantly increased (P<0.05), hairfollicles score was significantly lowered (P<0.05), anagen significantly delayed. On thenineteenth day after depilation, compared with Control mice, CRS mice skin turnedblack, skin grayscale ratio was significantly decreased (P<0.05), hair follicles score wasstill significantly lowered (P<0.05), catagen significantly delayed.2.(1) Compared withControl mice，the moving distance in3min of Open-field test in CRS, Tempol orRP67580treated mice were significantly decreased (P<0.05), plasmacorticosterone levels of CRS, Tempol or RP67580treated mice were significantly increased (P<0.05), which indicated the model of chronic restraint was successfulestablished.(2) Compared with Control mice, skin TBARS levels were increasedsignificantly (P<0.05), SOD and GSH-Px activity were decreased significantly in CRSmice (P<0.05); compared with CRS mice, skin TBARS levels were significantlyreduced and GSH-Px activity were significantly risen in Tempol or RP67580treatedmice (P<0.05).(3) On the ninth day after depilation, compared with CRS mice, Tempolor RP67580treated mice skin turn gray, skin grayscale ratio was significantly decreased(P<0.05), hair follicles score was significantly higher (P<0.05), anagen was not delayed;On the nineteenth day after depilation, compared with CRS mice, Tempol or RP67580treated mice skin turn gray, skin grayscale ratio was significantly increased (P<0.05),hair follicles score was significantly higher (P<0.05), catagen was not delayed.(4)Compared with Control mice, amount of SP+nerve fibers were increased significantlyin CRS mice (P<0.05), but significantly reduced in Tempol or RP67580treated micecompared with CRS mice (P<0.05).(5) Compared with Control mice, ratio ofdegranulated mast cells were increased significantly in CRS mice (P<0.05), butsignificantly reduced in Tempol or RP67580treated mice compared with CRS mice(P<0.05).Conclusion:：1. Chronic restraint stress delayed anagen of hair cycle.2. Chronicrestraint stress induced oxidative stress of skin.3. Chronic restraint stress activatedSP-MC pathway, increased amount of SP+nerve fibers and ratio of degranulated mastcells.4. There is an interaction between oxidative stress and SP-MC pathway.5.Application of antioxidant or SP receptor antagonist can partly ameliorate negativeeffects of CRS.6. Chronic restraint stress is an ideal model of research in relationshipbetween psychological stress and hair cycle.