丙酸氯倍他索通过影响p-STAT3和AKT表达的抗银屑病作用研究

Study on the anti-psoriasis effect of clobetasol propionate by affecting p-STAT3 and AKT expression

目的探讨丙酸氯倍他索对咪喹莫特诱导的银屑病小鼠磷酸化信号转导因子和转录激活因子3(p-STAT3)、蛋白激酶B(AKT)途径的影响。方法40只雌性小鼠随机分为4组:正常组、银屑病模型组(IMQ组)、预防性丙酸氯倍他索处理组(IMQ+pre-CLO组)、治疗性丙酸氯倍他索处理组(IMQ+thera-CLO组)。小鼠背部皮肤2 cm×3 cm面积脱毛,皮肤裸露,在脱毛部位涂抹咪喹莫特55 mg/只建立银屑病小鼠模型,每天1次。预防性丙酸氯倍他索处理组造模第1天起开始给药,治疗性丙酸氯倍他索处理组造模后第5天起开始给药,两种给药方式的丙酸氯倍他索剂量均为45 mg/只。第10天处理小鼠,皮肤组织切片进行HE染色,免疫组化法分析小鼠皮肤中p-STAT3、AKT、磷酸化AKT(p-AKT)以及白介素17A(IL-17A)的表达。结果与正常组小鼠相比,IMQ组小鼠皮肤出现明显鳞屑及红斑,表皮棘层明显增厚,炎症细胞浸润增加。与正常组比较,IMQ组皮损中的p-STAT3、AKT、p-AKT及IL-17A高表达(均P<0.05);丙酸氯倍他索处理后,与IMQ组小鼠相比,IMQ+pre-CLO组和IMQ+thera-CLO组小鼠症状显著改善,表皮厚度明显变薄,皮损组织中p-STAT3、AKT、p-AKT及IL-17A的表达均降低(均P<0.05)。结论丙酸氯倍他索可能通过抑制银屑病小鼠STAT3的磷酸化,减少炎症因子IL-17A的表达,降低AKT的磷酸化抑制角质细胞增殖,从而发挥抗银屑病作用。

Objective To explore the effect of clobetasol propionate on p-STAT3 and AKT pathway inpsoriatic mice induced by imiquimod.Methods The female mice(n=40)were arbitrarily divided into the following groups:normal group,IMQ group,preventiveclobetasol propionate group(IMQ+pre-CLO group),and therapeutic clobetasol propionate group(IMQ+thera-CLO group).Mice were depilated on a 2 cm×3 cm area of dorsal skin,the skin was exposed,and imiquimod 55 mg/only was applied to the depilated area to establish a psoriasis mouse model,once a day.The prophylactic clobetasol propionate-treated group was started from day 1 of modeling,and the therapeutic clobetasol propionate-treated group was started from day 5 after modeling,and the dosage of clobetasol propionate for both dosing modes was 45 mg/pup.Mice were treated on day 10,and skin tissue sections were subjected to HE staining,and the expression of phosphorylated signal transducer and activator of transcription 3(p-STAT3),protein kinase B(AKT),phosphorylated AKT(p-AKT),and interleukin 17A(IL-17A)was analyzed by immunohistochemistry in mouse skin.Results Compared with the normal group of mice,the skin of mice in the IMQ group showed obvious scales and erythema,obvious thickening of the epidermal stratum spinosum,and increased inflammatory cell infiltration.Compared with the normal group,p-STAT3,AKT,p-AKT and IL-17A were highly expressed in the skin lesions of the IMQ group(all P<0.05);after clobetasol propionate treatment,compared with the mice in the IMQ group,the symptoms of the mice in the IMQ+pre-CLO group and the mice in the IMQ+thera-CLO group were significantly improved,and the thickness of the epidermis was significantly thinned,and the skin lesion tissues contained p-STAT3,AKT,p-AKT and IL-17A expression were reduced(all P<0.05).Conclusion Clobetasol propionate may exert anti�psoriasis effects by inhibiting the phosphorylation of STAT3 in psoriasis mice,decreasing the expression of the inflammatory factor IL-17A,and reducing the phosphorylation of AKT to inhibit keratinocyte proliferation.