大麻二酚对咪喹莫特诱导的小鼠银屑病的改善作用

Ameliorating effect of cannabidiol on imiquimote-induced psoriasis in mice

目的探究大麻二酚对咪喹莫特诱导的小鼠银屑病炎症反应和氧化应激指标的改善作用。方法将BALB/c小鼠随机对照组、模型组、他克莫司组、大麻二酚(50、100、150 mg/kg)组,每组8只。除对照组小鼠外,其他组小鼠背部每日均匀涂抹62.5 mg的5%咪喹莫特诱导银屑病模型,造模4 h后,他克莫司组小鼠背部均匀涂抹他克莫司乳膏、大麻二酚组均匀涂抹50、100、150 mg/kg大麻二酚醇溶液,对照组、模型组背部均匀涂抹凡士林,1次/d,连续7 d每天拍照记录PASI评分。末次给药24 h后用酶联免疫吸附法检测皮肤组织中白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的含量;苏木精–伊红染色(HE)皮损组织;对小鼠脾脏就进行称量,并计算脾脏指数。检测小鼠的皮肤组织中超氧化物歧化酶(SOD)活性及谷胱甘肽(GSH)、丙二醛(MDA)含量。结果PASI评分及HE染色结果显示,与模型组比较,大麻二酚组可显著改善小鼠背部皮肤发红、增厚、皮屑增多等银屑病特征,小鼠背部皮肤表皮增厚现象明显减轻;脾脏指数显著降低(P<0.05、0.01)。在皮肤组织样本中,与模型组相比,大麻二酚组IL-6、TNF-α含量均明显降低(P<0.01、0.001);大麻二酚组能显著提高银屑病小鼠背部皮肤组织中SOD活力和GSH含量,降低MDA的含量(P<0.01、0.001)。结论大麻二酚对咪喹莫特引发的小鼠银屑病样炎症具有显著的抑制作用,并对炎症细胞的浸润和氧化应激状态等细胞因子的产生具有抑制作用。

Objective To investigate the therapeutic effect of cannabidiol on imiquimod-induced psoriatic inflammation and oxidative stress index in mice.Methods BALB/c mice were randomly assigned to control group,model group,tacrolimus group,and cannabidiol(50,100,150 mg/kg)groups,with 8 mice in each group.In addition to the control group,62.5 mg of 5%imiquimot-induced psoriasis model was evenly applied on the back of mice in other groups every day.4 h after modeling,tacrolimus group was evenly applied with Tacrolimus Cream,cannabidiol group was evenly applied with 50,100,150 mg/kg cannabidiol alcohol solution,control group and model group were evenly applied with petroleum jelly on the back.PASI score was recorded by taking photos once daily for 7 consecutive days.The contents of IL-6 and TNF-αin skin tissue were detected by enzyme-linked immunosorbent assay 24 h after the last administration.HE staining of skin tissue;the spleen of mice was weighed,and the spleen index was calculated.The activity of SOD and the contents of GSH,and MDA in the skin of mice were detected.Results PASI score and HE staining results showed that,compared with model group,cannabidiol group could significantly improve the characteristics of psoriasis such as redness,thickening and increased dander of the back skin of mice,and the epidermal thickening of the back skin of mice was significantly reduced.The spleen index was significantly decreased(P<0.05,0.01).In skin tissue samples,the contents of IL-6 and TNF-αin cannabidiol group were significantly decreased compared with model group(P<0.01,0.001).Cannabidiol group could significantly increase SOD activity and GSH content in the skin tissue of psoriasis mice,and decrease MDA content(P<0.01,0.001).Conclusion Cannabidiol significantly inhibited the psoriatic inflammation induced by imiquimod in mice,and inhibited the infiltration of inflammatory cells and the production of cytokines such as oxidative stress state.