淫羊藿苷通过抑制PI3K-AKT-血管增生治疗模型小鼠银屑病OA

Objective To explore the mechanism of icariin(ICA)in the treatment of psoriasis.Methods Thirty-six C57BL/6 mice were randomly divided into 6 groups with 6 in each:a blank(Ctrl)group,a model group,a positive control group treated with methotrexate,and experimental groups treated respectively with low,medium,and high doses of ICA.Ann imiquimod(IMQ)-induced psoriasis animal model was established.Methotrexate was given by intragastric administration at a concentration of 1 mg/kg.The animals in low,medium,and high dose ICA groups received intragastric administration of 0.4 mg/100 mL,0.8 g/100 mL and 1.2 g/100 mL respec-tively.On day 6 of the experiment,dorsal skin samples were collected from all six groups of mice for Hematoxy-lin-Eosin(HE)staining microscopy.RT-qPCR was used to measure the inflammatory level of Il-6,Il-17a and Tnf-α in the mouse skin.Immunofluorescence double staining was employed to observe CD31 and VEGF level in the mouse skin.Western blot was used to detect the protein level of PI3K,AKT,p-PI3K,and p-AKT in the mouse skin.Results Compared with the model group,the high-dose ICA group significantly improved IMQ-in-duced skin thickening(P＜0.000 1)and reduced the PASI score in mice.The high-dose ICA group significantly decreased mRNA level of Tnf-α,Il-6 and Il-17a in the skin of psoriasis mice(P＜0.000 1)and reduced the lev-el of CD31 and VEGF in the skin of psoriasis mice.Additionally,the high-dose ICA group reduced protein level of PI3K(P＜0.05),AKT(P＜0.05),p-PI3K(P＜0.05)and p-AKT(P＜0.01)in the mouse skin.Conclusions High-dose 1.2 g/100 mL ICA exhibits superior anti-psoriatic properties,with its mechanism poten-tially involving inhibition of PI3K-AKT-mediated angiogenesis.