Therapeutic Effect And Mechanism Of Qingre Qushi Recipe On Skin Lesions Of Th17-Dominated Atopic Dermatitis-Like Mice

Background: Atopic dermatitis(AD)is a chronic recurrent inflammatory dermatosis.Its pathological mechanism is not yet clear,but the abnormalities of Th17 play an important role in Asian AD patients.QRQS is a prescription of Chinese herbal medicine.Its main effect is to clear away heat and dampness.It is often used in alleviating skin inflammation and itching in our department.Its clinical effect is reliable.Objective: The aims of our study are to confirm whether QRQS has therapeutic effect on Th17-dominated AD,and discuss the possible mechanism.Materials and methods: Flaky tail mice are a spontaneous AD mouse model with the mutation of filaggrin.Inflammation occurs at the age of 8 weeks,AD-like lesions occur at the age of 28 weeks,and the most obvious lesions occur at the age of 32 weeks.After two weeks of treatment,the dermatitis score and scratching frequency of mice were assessed before and after treatment.Histological evaluation was made according to the pathological criteria.The serum levels of chemokines Ig E and Ig G1 were determined by ELISA.Flow cytometry was used to analyze the changes of T helper cell population in each group.The levels of Th17/Treg cells and Th2/Th1-related cytokines such as IL-2,IL-10,TGF-?,Fox P3,IL-6,ROR?-t,IL-17 A,IL-4,IL-5,GATA3,T-bet and IFN-gamma were determined by ELISA and RT-PCR.The phosphorylation levels of STAT5 and STAT3 proteins were quantified by Western blotting.Results:(1)Atopic dermatitis-like lesions were observed in ft mice at 32 W.Inflammatory cell infiltration was observed in the dermis.Th17 A expression was increased in the lesions and serum of ft mice.(2)QRQS can improve the dermatitis symptoms of AD mice,reduce dermatitis score and scratch frequency.(2)After QRQS treatment,Treg cell abnormalities were regulated,suppressed STAT5 was activated,and related regulatory T(Treg)cytokines such as IL-2,IL-10 and Fox P3 were up-regulated.(3)After QRQS treatment,STAT3 overexpression was inhibited,and related Th17 cytokines such as IL-6,ROR?-t and IL-17 A were also down-regulated.(4)After QRQS treatment,the expression of Th2 cytokines such as IL-4,IL-5 and GATA3 in serum and lesions was inhibited.(5)After QRQS treatment,Th1 cytokines such as T-bet and IFN-? were overexpressed in serum and lesions.Conclusion:(1)QRQS has therapeutic effect on Th17-dominated AD model mice and can improve the condition of mice.(2)QRQS may regulate the balance between Th17 and Treg cells via STAT3 and STAT5 pathways,thereby regulating the immune dysfunction to achieve therapeutic effects.