双氢青蒿素通过调节Th17/Treg平衡改善银屑病小鼠皮损机制研究

目的验证双氢青蒿素(DHA)是否能改善咪喹莫特(IMQ)诱导的银屑病小鼠皮损, 并探讨其可能的机制。方法24只雌性BALB/c小鼠随机分为4组:空白对照组(Control组)、模型组(Model组)、25 mg/kg DHA治疗组(DHA-L组)、50 mg/kg DHA治疗组(DHA-H组)，每组6只。每天观测小鼠皮肤变化并进行PASI评分。连续给药6 d，取小鼠皮肤进行HE染色和Ki67免疫组织化学染色；流式细胞仪检测小鼠脾Th17细胞和调节性T细胞(Treg)；ELISA检测小鼠血清白细胞介素17A(IL-17A)和肿瘤坏死因子-α(TNF-α)水平。结果IMQ成功诱导银屑病小鼠模型，DHA治疗后小鼠皮损改善，组织病理学改善，DHA-L和DHA-H组PASI评分及Ki67阳性细胞数量均低于Model组(P < 0.05)；Model组脾Th17细胞比例较Control组升高(P < 0.05)，DHA-L组和DHA-H组均较Model组降低(P < 0.05)；DHA-L组和DHA-H组脾Treg细胞比例较Model组升高(P < 0.05)；Model组血清IL-17A和TNF-α水平均较Control组升高(P < 0.05)，与Model组相比，血清IL-17A水平在DHA-L和DHA-H组均降低(P < 0.05)，而血清TNF-α水平仅DHA-H组降低(P < 0.05)。结论DHA可以改善IMQ诱导的银屑病小鼠皮损，其机制可能和调节Th17/Treg细胞平衡有关。

Dihydroartemisinin alleviates skin lesions in mouse of psoriasis by regulating Th17/Treg balance

ObjectiveTo evaluate whether dihydroartemisinin (DHA) can improve the skin lesions in mouse model of psoriasis induced by imiquimod (IMQ) and to further explore its mechanism.MethodsA total of 24 female BALB/c mice were randomly divided into control group, model group, DHA-L group (treated with 25 mg/kg DHA), and DHA-H group (treated with 50 mg/kg DHA), with 6 mice in each group.The skin lesions were observed every day and eavaluated by PASI score.After 6 days of continuous DHA therapy, the skin morphology was examined by HE staining and subjected to immunohistochemical staining with Ki67.The Th17 cells and Treg cells in spleen were investigated by flow cytometry, and interleukin-17A(IL-17A) and tumor necrosis factor-α (TNF-α) in serum were detected by ELISA.ResultsThe psoriatic mouse model was successfully induced by IMQ.After DHA treatment, both the skin lesions and pathological changes were improved, and the PASI score and Ki67 positive cells in the DHA-L and DHA-H groups were lower than those in the model group (P < 0.05).The proportion of splenic Th17 cells in the model group was higher than that in the control group (P < 0.05), and the proportion of Th17 cells in the DHA-L and DHA-H groups were lower than that in the model group (P < 0.05).The proportion of splenic Treg cells in the DHA-H group was higher than that in the model group (P < 0.05).The levels of IL-17A and TNF-α in the model group were higher than those in the control group (P < 0.05).The levels of IL-17A in the DHA-L and DHA-H groups were lower than those in the model group (P < 0.05), while the levels of TNF-α were lower only in the DHA-H group (P < 0.05).ConclusionsDHA can alleviate IMQ-induced skin lesions in mouse of psoriasis, and its mechanism may be related to regulating Th17/Treg cells balance.