熊果酸对咪喹莫特诱导的小鼠银屑病样皮损的影响

Effects of Ursolic Acid on Imiquimod-induced Psoriasis-like Lesions in Mice

目的探讨熊果酸(ursolic acid,UA)对咪喹莫特诱导的小鼠银屑病样皮损的影响及其可能通路。方法40只清洁级BALB/c雌性小鼠随机分为4组:正常对照组、模型组、UA低剂量组和UA高剂量组。模型组和UA组在背部和耳部外涂5%咪喹莫特,建立银屑病样皮损模型,建模第1天开始UA灌胃给药,连续6d,每天观察小鼠背部皮损情况并评分,测量耳朵厚度。在药物处理后第7天取材,用HE染色检测小鼠皮损组织病理学变化,免疫组化检测小鼠组织中IL-33,ST2,CD4及CD8表达。结果与正常对照组相比,模型组小鼠耳朵皮肤增厚,背部皮损出现鳞屑和红斑,组织学显示表皮增厚,表皮突延伸伴有角化不全、微脓肿。与模型组相比,UA组小鼠背部皮损鳞屑、红斑及增厚均明显缓解,UA高剂量组症状缓解更明显。免疫组化显示模型组皮损中IL-33,ST2,CD4及CD8较正常对照组表达显著增多,而UA低剂量组IL-33,ST2,CD4及CD8较模型组表达减少,UA高剂量组皮损中IL-33,ST2,CD4及CD8较模型组表达较少更明显。结论 UA可改善咪喹莫特诱导的小鼠银屑病样皮损的发生和发展,其机制可部分通过调节T淋巴细胞和IL-33而实现。

Objective To evaluate effects of UA on imiquimod- induced psoriasis-like lesions in mice and its possible mechanisms. Methods Forty female BALB/c mice were randomly divided into 4 groups： control, model, low-dose UA and high-dose UA group. Psoriasis-like lesions were induced by daily application of 5% imiquimod to both the back and ears of mice for 6 days. Mice in UA group were intragastrieally given UA while being treated with 5% imiquimod. The changes in the back skin lesions were observed and scored, and the thickness of the ears was also measured. On the seventh day, skin biopsies were taken for HE staining and immunohistochemical staining of IL-33, ST2, CD4 and CD8. Results Compared with the control group, increased ear thickness, and erythema and scales on the back of the mice were observed in model group; Pathological changes of back skin lesion included epidermal thickening, elongation of rete ridges, and microabscess along with parakeratosis. However, UA treatment, particularly at high dose, attenuated imiquimod-induced changes in erythema, scales and the epidermal thickness. Moreover, the expression levels of IL-33, ST2, CIM and CD8 were higher in lesions of model group in comparison with the control group. Furthermore, UA treatments reduced the expression levels of IL-33, ST2, CD4 and CD8 in imiquimod-treated skin. More dramatic reductions in IL-33, ST2, CD4 and CD8 expression were observed after treatments with high-dose UA. Conclusion UA could alleviate imiquimod-induced psoriasis-like lesions possibly through modulating T lymphocytes and IL-33.