D-松醇调节Notch1/Hes1信号通路对银屑病皮损大鼠Th1/Th2平衡的影响

doi:10.3969/j.issn.1006-6233.2023.03.05

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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.

Key words： D-pinitol Psoriasis Notch 1 Hairy and enhancer of split 1 pathway T helper cell 1 T helper cell 2

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2023.03.05 OR http://www.hbyxzzs.cn/EN/Y2023/V29/I3/375

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