丹皮酚通过抑制树突状细胞活性在咪喹莫特诱导的银屑病皮肤病中的作用研究

Effects of Paeonol in Psoriasis Induced by Imiquimod by Inhibiting Activity of Dendritic Cells

目的探究丹皮酚对树突状细胞(DCs)抑制作用,及对咪喹莫特(IMG)诱导的银屑病模型小鼠炎症反应的干预效果。方法选择BALB/c雄性小鼠作为实验用鼠,按照随机数字表法平均分为6组,分别为空白对照组(Con组)、模型对照组(IMQ组)、甲氨蝶呤阳性组(MTX组)及丹皮酚高(PG-H)、中(PG-M)、低(PG-L)剂量组,每组10只。通过模型建立及药物干预,以及BMDCs骨髓细胞分离及体外诱导培养,比较皮损组织白细胞介素(IL)-23、CD11c及CD3的表达水平,以及体外细胞实验对DCs细胞IL-23、IL-1β、IL-12p40 m RNA的表达水平综合评价丹皮酚对咪喹莫特诱导的银屑病的干预效果。结果皮损组织CD3^+表达水平方面,丹皮酚各剂量之间差异无统计学意义,与MTX组效果一致。皮损组织IL-23表达水平方面,高剂量效果最显著,差异有统计学意义(P<0.05)。体外实验中,丹皮酚直接作用于BMDCs,IL-23 mRNA表达明显降低(P<0.05),而对IL-1β、IL-12p40 m RNA的影响差异无统计学意义(P>0.05)。结论丹皮酚可有效减轻咪喹莫特诱导的银屑病局部皮损,作用机制可通过减弱IL-23 m RNA表达,抑制了树突细胞的成熟和活化,最终减轻了银屑病的皮肤损伤。

Objective In order to investigate the inhibitory effects of Paeonol on dendritic cells(DCs)and the effects of IMG induced inflammatory reaction in the psoriasis model mice.Methods BALB/c male mice were selected as the experimental mice,and divided into six groups blank control group(group Con)model control group(group IMQ),methotrexate positive group(group MTX),and paeonol high(PG-H),middle(PG-M),low(PG-L)dosage group,10 mice in each group.The expression levels of interleukin IL-23,CD11c and CD3 in skin lesions were compared by model establishment,drug intervention,BMDCs bone marrow cell isolation and in vitro induction culture.The intervention effects of Paeonol on imiquimod induced psoriasis according to the random number table method including were evaluated by the expression level of IL-23,IL-1 beta and IL-12p40 mRNA in DCs cells in vitro.Results There were no statistical differences between the different doses of Paeonol in the level of CD3+expression in skin lesions,which was consistent with the effects of MTX group.The high dose effect was the most significant in the level of IL-23 expression in skin lesions,and the difference was statistically significant(P<0.05).In vitro experiment,paeonol acted directly on BMDCs,and the expression of IL-23 mRNA decreased significantly(P<0.05),but there was no significant difference in the effects of IL-1 and IL-12p40 mRNA(P >0.05).Conclusion Paeonol can effectively reduce the local lesions of psoriasis induced by imiquimod.The mechanism of action can reduce the expression of IL-23 mRNA,inhibit the maturation and activation of dendritic cells,and ultimately reduce the skin damage of psoriasis.