Sulforaphane Regulates Nrf2-mediated Oxidative Stress And NLRP3 Inflammatory Pathway To Prevent And Treat Radiation-induced Skin Injury

ObjectiveTo observe the protective effect of sulforaphane(SFN)on radiationinduced skin injury(RISI).The mechanism of SFN in the prevention and treatment of RISI will be discussed.MethodsA total of 24 mice aged 8 weeks were selected as the experimental animals.After 1 week of adaptive feeding,The left thigh of mice was irradiated at a time under intravenous anesthesia to establish a RISI model.The mice were randomly allocated into four groups,including the control,SFN,irradiation(IR)and IR plus SFN(IR/SFN)groups.The mice in the SFN and IR/SFN groups were subcutaneously given with SFN at 0.5 mg/kg daily in five days of each week for 4 weeks,while the mice in the IR group were received with irradiation plus equal amount of normal saline.According to the corresponding time after irradiation,the skin depilation and damage changes of the mice in each group were observed and recorded in detail.The morphological changes of mouse skin tissues were detected by H&E staining.Then the oxidative stress indexes such as 4-HNE and 3-NT and inflammatory response indexes such as NLRP3,caspase-1 and IL-1? in mouse skin tissues,as well as the expression of Nrf2 and its downstream antioxidant genes HO-1 and CAT were detect by Western blotting and real-time PCR.ResultsThe results of H&E staining showed that in the mouse skin tissues of IR group,the fibrous tissue hyperplasia,irregular arrangement of collagen fiber bundles,hyperplasia of adipose tissue and proliferating blood vessels could be observed.These obvious pathological features were not detected in the control and SFN groups.In the IR/SFN group,only a little fibrous tissue hyperplasia was observed,and other pathological changes were not obvious.Western blotting and real-time PCR results showed that the inflammatory indicators NLRP3,caspase-1 and IL-1? as well as oxidative stress damage indicators 4-HNE and 3-NT in the skin tissues of mice in the IR group increased significantly,comparing with the control group(P < 0.05).However,the above indexes declined sharply after SFN treatment(P < 0.05).In addition,the expressions of Nrf2 and its downstream antioxidant genes HO-1 and CAT were higher in the skin tissues of SFN and IR/SFN groups,but lower in the control and IR groups(P < 0.05).ConclusionSFN can suppress the oxidative stress damage by up-regulating the expression and function of Nrf2,and the inflammatory response by inhibiting the NLRP3 inflammatory pathway,so as to prevent and alleviate the RISI.