Study On The Therapy Effects And Autophagy Mechanism Of Narrowband Ultraviolet B On Patients With Vitiligo

Background There is significant effects on patients with vitiligo by treatment with narrow band UVB(NB-UVB).NB-UVB can promote melanocyte proliferation,melanogenesis and migration,but the specific mechanism was not fully elucidated.Autophagy is an important metabolic process of eukaryotes by which the damaged proteins,organelles are delivered to lysosome for degradation to maintain normal physiological function.Studies have confirmed there is dysfunction of autophagy in melanocytes of patients with vitiligo,so it is promising for the treatment of vitiligo to restore normal physiological function of melanocytes by inducing autophagy.However,it is not clear whether NB-UVB irradiation can regulate autophagy of melanocytes and play a role in the treatment of vitiligo by inducing autophagy of melanocytes.Objective To observe the clinical effects of narrow band UVB(NB-UVB)in the treatment of vitiligo and explore the treatment mechanism of autophagy induction of NB-UVB on vitiligo.Methods Thirty patients with non-segmental vitiligo were randomly selected from clinic and irradiated with NB-UVB twice a week for 20 times.Then,clinical effect was evaluated.The normal human melanocytes were irradiated with NB-UVB at varying single dose of 50,100 or 200mJ/cm~2 and the non-irrradiation melanocytes were as the controls.24 hours after irradiation,the autophagy levels of melanocytes were determined by monodansvlcadaverin(MDC)staining method.The protein expressions of p-AMPK,p-mTOR,LC3?/?and P62 were detected by western blot analysis.Transmission electron microscopy was performed to observe the ultrastructural changes of autophagosomes and melanosome in melanocytes.Results There was significant therapy effect on patients with vitiligo by treatment with NB-UVB irradiation for 20 times and the effective rate was 66.7%.MDC staining showed that the positive ratios of autophagosomes in melanocytes were significantly different among the four groups(F=37.880,P<0.05),and the positive ratios of the 100and 200 mJ/cm~2 groups were significantly increased compared with the control group and 50mJ/cm~2 group(q=6.746,10.684,5.550,8.481,both P<0.05).Western blot analysis revealed significant differences in the protein expressions of p-AMPK,p-mTOR,LC3?/?and P62 among the four groups(F=37.032,105.051,41.807,25.619,all P<0.05).Compared with the control group,the expressions of p-AMPK and LC3?/?were significantly increased in the 100 and 200mJ/cm~2 group(q=17.342,13.378,8.404,8.508,all P<0.05),while the expressions of p-mTOR and P62 were significantly decreased(q=7.467,11.344,6.294,5.549,all P<0.05).Significant differences were also observed in the number of melanosomes,autophagosomes and autophagolysosomes among the four groups(H=20.731,23.583,both P<0.05).Comparedwiththecontrolgroup,the numberof autophagosomesand autophagolysosomes were significantly increased in the 100 and 200mJ/cm~2 group(Z=3.259,3.305,both P<0.05).Meanwhile,the number of melanosomes were significantly higher in the 50,100 and 200mJ/cm~2 group than the control group(Z=3.366,3.368,3.366,all P<0.05).Conclusion NB-UVB irradiation is of great effective for patients with vitiligo.NB-UVBirradiationcanpromotetheformationofautophagosomesand autophagolysosomes of human melanocytes by activating autophagy signal pathway,which may be part of the mechanism in the treatment of vitiligo by NB-UVB.