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  

Influence of D-pinitol Modulation of Notch1/Hes1 Signaling Pathway on Th1/Th2 Balance in Rats with Psoriatic Skin Lesions

作　　者：马敬[1] 冯世军[1] 刘远 李泊辰 艾东方[1] 杨秀芳[1] MA Jing;FENG Shijun;LIU Yuan(Cangzhou Central Hospital,Hebei Cangzhou 061001,China)

机构地区：[1]河北省沧州市中心医院皮肤性病科,河北沧州061001

出　　处：《河北医学》2023年第3期375-380,共6页Hebei Medicine

基　　金：河北省医学科学研究课题计划项目,(编号:No.20200329)。

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。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 pr

关 键 词：D-松醇 银屑病 缺刻基因1 发状分裂相关增强子通路 辅助性T细胞1 辅助性T细胞2 

分 类 号：R758.63[医药卫生—皮肤病学与性病学]