Study On The Therapeutic Effect And Mechanism Of Mongolian Medicine Lideri-7 On Imiquimod-Induced Psoriasis In Mice

Objective: Through this experiment,we established imiquimod(Imiquimod,IMQ)-induced psoriasis mouse model to explore the therapeutic effect of LDR-7 on psoriasis and elucidate the mechanism of action of LDR-7 in treating psoriasis,to provide scientific basis for the clinical application of this drug.Methods: Seventy-two ICR mice were randomly divided into control group,model group,LDR-7 low-dose group,LDR-7 medium-dose group,LDR-7 high-dose group,and positive drug group(MTX).The mice were shaved(2 × 3 cm2)and coated with the drug.62.5 mg of Vaseline was applied to the back of the control mice daily,and 62.5 mg of imiquimod cream was applied to the back of the mice in the remaining groups for 9 days,and the mice were observed and recorded daily.After treatment with different concentrations of LDR-7,the effect of the drug on the skin lesions on the back of the mice was observed visually,and the skin lesions on the back of the mice were scored using the psoriasis area and severity index(PASI)scale.After the mice were executed on the 10 th day,the spleen weight and body weight were weighed and the spleen index was calculated,and the spleen index = spleen weight(mg)/mouse body weight(g).The effect of LDR-7 on the skin histopathology of psoriasis-like mice was observed by hematoxylin-eosin staining(HE).The changes of cytokines such as IL-17 and TNF-α in the serum of psoriasis-like mice were measured by ELISA,and the changes of protein expression related to TLR4/NF-κB signaling pathway,IL-17 signaling pathway and JAK/STAT3 signaling pathway in the skin of mice were detected by Western blotting.The changes of Ki67 and PCNA in the skin of mice were measured by immunohistochemistry to further investigate the therapeutic mechanism of LDR-7 in IMQ-induced psoriasis mice.Results: Daily application of imiquimod induced psoriasis-like lesions in a psoriasis mouse model,and the results showed that LDR-7 significantly improved the manifestation of dorsal lesions in mice,resulting in lighter erythematous color,less scaling and reduced lesion thickness,PASI score also showed the same result.Compared with the control group,the spleen index of the model group was significantly higher with statistical difference(p <0.01),and the spleen index of the LDR-7 high-dose group was lower than that of the model group with statistically significant difference(p < 0.05),while the differences between the LDR-7 low and medium-dose groups and the positive group were not statistically significant compared with the model group.As observed by HE-stained pathological sections,the model group mice had significantly thickened epidermis,hypertrophy of the spinous layer as well as extensive inflammation in the skin tissue.Compared with the model group,the epidermal thickness was significantly reduced in the LDR-7medium-dose group,high-dose and MTX group,hyperkeratosis and spiny layer hypertrophy were significantly improved,and local vasodilation and inflammatory cell infiltration were also reduced.The changes of Ki67 and PCNA in the skin tissues of mouse back were detected by immunohistochemistry,and the results showed that the expression of Ki67 and PCNA in the skin tissues of mice in the model group was significantly higher compared with the control group.Compared with the model group,the expression of Ki67 and PCNA in the skin tissues of mice in each LDR-7 group and positive group was significantly decreased.The cytokine changes of IL-17 and TNF-α in the serum of mice in each group were measured by ELISA,and the results showed that LDR-7 decreased the levels of IL-17 and TNF-α in the peripheral blood of IMQ-induced psoriasis mice.Western blotting was used to detect the changes of TLR4/NF-κB signaling pathway,IL-17 signaling pathway,and JAK/STAT3 protein expression in the dorsal skin of mice,and the results showed that LDR-7 could effectively inhibit the activation of TLR4/NF-κB,IL-17 and JAK/STAT3 signaling pathways.Conclusion: 1.ICR mice were successfully induced with psoriasis-like lesions by topical imiquimod on the back.2.The monoclonal drug LDR-7 had a therapeutic effect on imiquimod-induced psoriasis mouse model,reducing PASI score,lowering spleen index,improving pathological structural features,and reducing Ki67 and PCNA expression.3.LDR-7 inhibited serum levels of TLR4/NF-κB,IL-17,TNF-α levels and inhibited the activation of IL-17 and JAK/STAT3 signaling pathway.