The Mechanism And Preventive Study Of Airborne Particulate Matters Inhibiting Skin Barrier Repair By Aryl Hydrocarbon Receptor

Backgroud: Over the past few years,the frequent occurrence of urban hazy had caused widespread concern.The particulate matters carrying polycyclic aromatic hydrocarbons are one of the major pollutants that threaten people's health.Epidemiological studies in recent years had pointed out that particulate matters exposure induce and aggravate various skin diseases.The children with weak skin barriers and people with sensitive skin and skin diseases are susceptible population.Scholars speculate that the aggravation and recurrence of this condition may be related to inhibition of skin barrier repair and the occur of chronic epidermal inflammation.However,there is currently a lack of relevant experimental research about its toxicological mechanism.Methods: This study was divided into two parts.One is the preliminary study on the effects of short-term exposure of particulate matters on rat skin barrier repair and its toxicological mechanism.First,a rat model of skin barrier injury was constructed,then particulate matters exposure for 5 days.The detection of transdermal water loss,histological examination was performed to observe changes in skin barrier function and skin pathology.Electron microscopy combined with spectrometer to locate the particulate matters in skin.The possible mechanisms of action of particulater particles were explored by western blot of inflammatory related proteins.The second is the experimental study on the use of 3'-methoxy-4'-nitroflavone to prevent the biological toxicity of particulate matters on both HaCaT cells and rat skin.DCFH-DA probe assay,comet assay,TUNEL and qRT-PCR were performed to analysis its possible mechanism.The effect of 3'-methoxy-4'-nitroflavone on air pollutant particle damage was observed by skin barrier and histological examination.Results:Short-term exposure with air pollutant particles on the skin of rats with damaged barrier function can not only inhibit skin barrier repair,but also lead to parakeratosis,epidermal cell edema and other pathological changes.The toxicological mechanism may be as follows: particulate matters enter into the barrierdamaged epidermis,activate the aryl hydrocarbon receptors on the epidermal cells,then induce dermatitis through oxidant stress injury.The aromatic hydrocarbon receptor antagonist 3'-methoxy-4'-nitroflavone can competitively antagonize the aryl hydrocarbon receptor on HaCaT cells and inhibit the cytotoxicity of the particulate matters.Finally,we pretreated rat skin with 3'-methoxy-4'-nitroflavone in the form of a barrier cream before the exposure of particulate matters,.Epidermal cell edema was reduced,and skin barrier repair was accelerated.However,the remodeling of the stratum corneum is still unsatisfactory,which may be related to the rejection reaction from particulate matters.Conclusion: Particulate matters directly penetrate the damaged skin barrier,inducing dermatitis by oxidant stress injury.3'-methoxy-4'-nitroflavone can attenuate oxidant stress induced by particulate matters via competitively antagonizing the aryl hydrocarbon receptor on HaCaT cells.