湿润烧伤膏对寻常型银屑病小鼠IL23/Th17轴及其相关因子表达水平的影响

Effect of MEBO on the Expression Levels of IL23/Th17 Axis and Its Related Factors in Mice with Psoriasis Vulgaris

目的观察湿润烧伤膏(moist exposed burn ointment,MEBO)对咪喹莫特诱导的寻常型银屑病小鼠皮损组织中白细胞介素-17 (IL-17)、白细胞介素-23 (IL-23)、肿瘤坏死因子-α(TNF-α)及干扰素-γ(IFN-γ)水平的影响,并探讨其作用机制。方法选取40只SPF级健康雌性6~7周龄近交系BALB/c小鼠建立咪喹莫特诱导的寻常型银屑病模型,模型建立成功后采用随机数表法将35只小鼠随机分为对照组、模型组、MEBO低剂量组、MEBO中剂量组及MEBO高剂量组,并分别采用卡泊三醇乳膏、麻油、1:3湿润烧伤膏与麻油混合物、1:1湿润烧伤膏与麻油混合物、湿润烧伤膏处理皮损创面,治疗第7、14天参照银屑病皮损面积与严重程度指数(psoriasis area and severity index,PASI)评分标准评估5组小鼠皮损严重程度,治疗第14、28天采用Western blotting法检测IL-17、IL-23、TNF-α及IFN-γ蛋白表达水平,并予以对比。结果治疗第7天,对照组、MEBO中剂量组及MEBO高剂量组小鼠背部皮损PASI评分均显著低于模型组和MEBO低剂量组(P均<0.05),且对照组、MEBO中剂量组及MEBO高剂量组组间两两对比,PASI评分均无明显差异(P均>0.05);治疗第14天,5组小鼠皮损症状均明显改善,PASI评分无明显差异(P>0.05);治疗第14天,小鼠背部皮损组织中IL-17、IL-23、TNF-α及IFN-γ蛋白表达水平对比,对照组显著低于其他各组(P均<0.05),且MEBO高剂量组显著低于模型组(P均<0.05);治疗第28天,小鼠背部皮损组织中IL-17、IL-23、TNF-α及IFN-γ蛋白表达水平对比,对照组显著低于模型组、MEBO低剂量组及MEBO中剂量组(P均<0.05),与MEBO高剂量组无明显差异(P均>0.05),MEBO高剂量组和MEBO中剂量组显著低于模型组和MEBO低剂量组(P均<0.05),且MEBO高剂量组与MEBO中剂量组无明显差异(P均>0.05)。结论湿润烧伤膏治疗银屑病的疗效与卡泊三醇软膏相当,且调节IL-23/Th17轴及其相关因子的表达水平,抑制炎症反应可能是其作用机制。

Objective To observe the effect of MEBO on the levels of interleukin-17(IL-17),interleukin-23(IL-23),tumor necrosis factor-α(TNF-α) and interferon-γ(IFN-γ) in mice with psoriasis vulgoriasis induced by Imiquimod(IMQ) and explore its mechanism of action.Methods Forty 6-to 7-week-old specific-pathogen free(SPF)healthy inbred BALB/c female mice were selected and imiquimod-induced psoriasis vulgaris models were established on them.After the models were established,35 of them were randomly divided into a control group,a model group,a MEBO low-dose group,a MEBO medium-dose group and a MEBO high-dose group and their skin lesions were treated with calcipotriol cream,sesame oil,mixture of MEBO and sesame oil at the ratio of 1:3,mixture of MEBO and sesame oil at the ratio of1:1 and MEBO respectively.On day 7 and 14 of treatment,the severity of skin lesions of the five groups of mice were evaluated based on psoriasis area and severity index(PASI) scoring system.On day 14 and 28 of treatment,Western blotting was used to detect the protein expression levels of IL-17,IL-23 TNF-α and IFN-γ,which were then compared among each other.Results On day 7 of treatment,the PASI scores of the skin lesions on the backs of mice in the control group,the MEBO medium-dose group and the MEBO high-dose group were significantly lower than the model group and MEBO low-dose group(all P <0.05).Pairwise comparisons in PASI scores were made among the control group,the MEBO medium-dose group and the MEBO high-dose group and the results(all P> 0.05) showed no significant difference;on day 14 of treatment,the skin lesions on the backs of the five groups of mice improved significantly and no significant difference was observed in PASI scores(P> 0.05);on day 14 of treatment,the protein expression levels of IL-17,IL-23,TNF-α and IFN-γ in skin tissues on the backs of the mice were compared:their levels in the control group was significantly lower than other groups(all P <0.05) and their levels in the MEBO high-dose group was significantly lower than the model group(all P <0.05);on day 28 of treatment,the protein expression levels of IL-17,IL-23,TNF-α and IFN-γ in the skin tissues on back of the mice were compared:their levels in the control group was significantly lower than the model group,the MEBO low-dose group and the MEBO medium-dose group(all P <0.05) and no significant difference was observed between the levels of the control group and MEBO high-dose group(all P> 0.05);their levels in the MEBO high-dose group and the MEBO medium-dose group were significantly lower than the model group and the MEBO low-dose group(all P <0.05),and no significant difference was observed between the MEBO high-dose group and the MEBO medium-dose group(all P>0.05).Conclusion MEBO has similar effect with calcipotriol cream in treating psoriasis.Their mechanism of action may lie in their ability to regulate the expression of IL-23/Th17 axis and its related factors,and inhibit inflammatory reactions.