The Efficacy And Mechanism Of N-3 Polyunsaturated Fatty Acid Protect Skin From Ultraviolet Induced Acute Injury Based On SKH-1 Hairless Mouse Model

Background Acute light injury caused by ultraviolet(Ultraviolet,UV)can occur within hours to a few days after sunlight exposure.Acute light damage manifests as erythema or sunburn.It can cause immunosuppression and induce phototoxic reaction,photosensitive reaction or solar related dermatitis.Besides inducing inflammation of skin,UV also destroys skin barrier.In histology level,UV can cause vasodilatation,inflammatory cell infiltration,sunburn cell formation and intercellular edema.At molecular level UV induced a large number of reactive oxygen species(Reactive oxygen species,ROS)stimulate inflammation related cytokines in keratinocyte,such as tumor necrosis factor-?(TNF-?),interleukin-1?(Interleukin-1?),interleukin-6(IL-6)and interleukin-4(IL-4).So far,the mainly UV protection methods are physical shading and sunscreen usage.However,the above methods are time-consuming and labor-intensive,and many people cannot apply the correct sun protection methods frequently.Several researchers and the public both focus on dietary supplement to protect skin from UV.N-3 polyunsaturated fatty acids(n-3 PUFA)are also precursors of eicosanoids,which can compete with n-6 PUFA on the cell membrane for arachidonic acid(AA)metabolism pathway.Thereby,n-3 PUFA reduce the inflammation related factors and immune related molecules from AA metabolism pathway and inhibit inflammatory reaction.Whether dietary supplementation with n-3 PUFA can reduce skin damage caused by UV is not well studied.The dosage-effect and the mechanism also need more exploration.Objective In this study,we examined the protective effect of n-3 PUFA for UV induced skin light damage on SKH-1 hairless mice.We also determined the effective dose and explored its mechanism.Method We designed 5 kinds of special chows containing different ratio of n-3 PUFA and n-6 PUFA(n-3/n-6 PUFA: 0%/100%,12.5%/88.5%,25%/75%,50%/50%,100%/ 0%)for mice.The rest nutrients were same as regular chows.At the second week,fourth week and eighth week of the special diet,10 mice in each group were treated with UV on skin to induce acute light damage and other 5 mice were negative control.Skin swelling and desquamation were observed after 24 hs.Biopsies were taken for pathological examination.Intercellular edema,infiltration of inflammatory cells and sunburn cells were evaluated after HE staining.The skin barrier function was measured,including the transepidermal water loss(TEWL)and skin water content.Immunohistochemistry was used to observe the expression of IL-1,IL-6 and TNF-alpha in the skin tissues.Inflammatory cytokines including TNF-?,IL-1 ?,IL-6 and IL-4 were detected by real-time PCR and Enzyme linked immunosorbent assay(ELISA).Result After eighth week of special diet,dermascopy and gross observation showed that the degree of acute skin damage in mice with n-3 PUFA content of 25%,50% and 100% was less than that of 0% and 12.5% groups.Histology showed that the skin,dermis and subcutaneous tissue of the mice without UV were clear,and the epidermis was uniform,and there was no difference between the different diet groups.After 24 hours of UV,mice with n-3 PUFA content of 25%,50% and 100% showed thicker epidermis,more severe intercellular edema and infiltration of inflammatory cells compared with 0% and 12.5% groups.After UV,the TEWL value in all mice was increased and the water content was decreased.In the group with higher n-3 PUFA content,the TEWL increased was less and the skin moisture content was higher,and the skin barrier damage was less.Molecular biological detection showed that the m RNA and protein expression of IL-1 ?,TNF-?,IL-4 and IL-6 was lower after ultraviolet irradiation in higher n-3 PUFA content group(P < 0.05).At the second week and fourth week,the results showed the similar trend with the eighth week.Conclusion Dietary supplementation of n-3 PUFA has protective effect on UV induced acute light injury.N-3 PUFA content needs to reach more than 25% of total fatty acid content,and the higher the content,the stronger the protective effect.