【摘要】 目的:探索D-松醇对银屑病皮损大鼠Th1/Th2平衡影响的机制研究。方法:构建咪喹莫特(IMQ)大鼠模型，随机分为对照组、IMQ组、D-松醇低剂量组、D-松醇中剂量组、D-松醇高剂量组和阳性对照组，每组10只。造模成功后大鼠给与D-松醇低、中、高剂量组(50mg/kg、100mg/kg、150mg/kg)和阳性对照组(1mg/kg,甲氨蝶呤)灌胃治疗，对照组和IMQ组给予相同剂量的生理盐水，每天一次，连续7d。在给药第8天对各组大鼠银屑病皮损症状和指数(MPASI)评价；HE染色观察银屑病皮损病理变化；ELISA检测血清中干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、白介素-4(IL-4)、白介素-10(IL-10)水平；以流式细胞术检测辅助性T细胞1(Th1)/辅助性T细胞2(Th2)比值；Western blot检测T盒子转录因子(T-bet)、GATA结合蛋白3(GATA-3)、缺刻基因1(Notch1)、发状分裂相关增强子1(Hes1)蛋白表达。结果:与对照组比较，IMQ组大鼠皮肤出现银屑病样病变如红斑、过度角质化、炎性细胞浸润等，IFN-γ、TNF-α、Th1细胞、T-bet、Notch1、Hes1水平显著升高(P<0.05),IL-4、IL-10、Th2细胞、GATA-3水平显著降低，Th1/Th2细胞比例失衡(P<0.05);经D-松醇治疗后，大鼠银屑病样病变减轻或消失，皮损指数下降，IFN-γ、TNF-α、Th1细胞、T-bet、Notch1、Hes1水平下降(P<0.05),IL-4、IL-10、Th2细胞、GATA-3水平升高，Th1/Th2比例有所恢复(P<0.05)。结论:D-松醇可能通过抑制Notch1/Hes1信号通路调节Th1/Th2平衡，降低炎性因子产生，减轻IMQ大鼠银屑病皮损。更多还原

【Abstract】 Objective: To explore the mechanism of the influence of D-pinitol on Th1/Th2 balance in psoriatic skin lesions in rats. Methods: The imiquimod(IMQ) rat model was constructed and randomly grouped into control group, IMQ group, low-dose D-pinitol group, medium-dose D-pinitol group, high-dose D-pinitol group and positive control group, 10 in each group. After successful modeling, the rats were given intragastric administration of D-pinitol low, medium and high dose groups( 50 mg/kg, 100 mg/kg, 150 mg/kg) and positive control group( 1 mg/kg, methotrexate). The control group and IMQ group were given the same dose of normal saline once a day for 7 days.On the 8th day of administration, different drug treatments were given to evaluate the psoriasis skin lesion symptoms and index(MPASI) of rats in each group; HE staining was used to observe the pathological changes of psoriatic skin lesions; ELISA was applied to detect serum levels of interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), interleukin-4(IL-4), and interleukin-10(IL-10); flow cytometry was used to measure the T helper 1(Th1)/helper 2(Th2) ratio; Western blot was applied to detect the protein expressions of T box transcription factor(T-bet), GATA-binding protein 3(GATA-3), Notch 1 and hairy and enhancer of split 1(Hes1). Results: Compared with the control group, the rats in the IMQ group had psoriasis-like lesions such as erythema, hyperkeratinization, inflammatory cell infiltration, etc. the levels of IFN-γ, TNF-α, Th1 cells, T-bet, Notch1 and Hes1 were obviously increased(P<0.05), the levels of IL-4, IL-10, Th2 cells, and GATA-3 were obviously reduced, the ratio of Th1/Th2 cells was unbalanced(P<0.05); after D-pinitol treatment, the psoriasis-like lesions in rats were alleviated or disappeared, and the skin lesion index decreased, the levels of IFN-γ, TNF-α, Th1 cells, T-bet, Notch1 and Hes1 decreased(P<0.05), the levels of IL-4, IL-10, Th2 cells, GATA-3 increased, Th1/Th2 ratio recovered somewhat(P<0.05). Conclusion: D-pinitol may inhibit Notch1/Hes1 signaling pathway to regulate Th1/Th2 balance, reduce the production of inflammatory factors, and alleviate psoriatic skin lesions in IMQ rats.更多还原