富马酸二甲酯调节巨噬细胞极化状态对原发免疫性血小板减少症小鼠的治疗效果  

Therapeutic effect of dimethyl fumarate on regulating polarization state of macrophages in mice with primary immune thrombocytopenia

作　　者：宋传龙 焦红杰 海力其古丽·努日丁[1] 赵莉[1] 严媚[1] SONG Chuanlong;JIAO Hongjie;HAILIQIGULI·Nuriding;ZHAO Li;YAN Mei(Pediatric Department 1,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院儿内一科,乌鲁木齐830054

出　　处：《中国免疫学杂志》2023年第10期2021-2027,共7页Chinese Journal of Immunology

基　　金：国家自然科学基金资助项目(82160031)。

摘　　要：目的:探究富马酸二甲酯(DMF)通过调节巨噬细胞极化影响原发免疫性血小板减少症(ITP)的作用。方法:将BALB/c小鼠分为对照组、ITP组、DMF低剂量组和DMF高剂量组,每组15只,除对照组外,其余3组小鼠均构建ITP模型,DMF低、高剂量组小鼠分别以10 mg/kg、20 mg/kg DMF灌胃,1次/d,连续14 d;全自动血细胞分析仪检测小鼠外周血血小板(PLT)、红细胞(RBC)、白细胞(WBC)以及血红蛋白(Hb)水平;ELISA法检测小鼠血清IFN-γ、IL-2、IL-4、IL-10、IL-17及TGF-β1水平;电子天平称量小鼠体质量、脾脏、胸腺,计算脏器指数;HE染色观察小鼠脾脏组织和骨髓组织内巨核细胞数目;免疫荧光染色检测小鼠脾脏组织内巨噬细胞极化情况;流式细胞术测定小鼠外周血中巨噬细胞极化情况。结果:同一时间点下造模小鼠外周血血小板数量较对照组小鼠明显下降(P<0.05),说明造模成功;造模后,与对照组比较,ITP组小鼠PLT、RBC及Hb均下降,WBC升高(P<0.05),血清中IFN-γ、IL-2及IL-17均升高,TGF-β1、IL-4及IL-10均下降(P<0.05),脾脏指数升高(P<0.05),脾脏与骨髓中巨核细胞数目均增加(P<0.05),脾脏组织内M1型巨噬细胞标记CD68^(+)CD86^(+)阳性表达率升高,M2型巨噬细胞标记CD68^(+)CD206^(+)阳性表达率降低(P<0.05),外周血内F4/80^(+)CD86^(+)标记细胞比例升高,F4/80^(+)CD206^(+)标记细胞比例则降低(P<0.05);与ITP组比较,DMF低剂量组小鼠PLT升高,WBC下降(P<0.05),DMF高剂量组小鼠PLT、RBC及Hb均升高,WBC下降(P<0.05),DMF低、高剂量组血清中IFN-γ、IL-2及IL-17均下降,TGF-β1、IL-4及IL-10均升高(P<0.05),脾脏指数降低(P<0.05),脾脏与骨髓中巨核细胞数目也均减少(P<0.05),此外,脾脏组织内CD68^(+)CD86^(+)阳性表达率降低,CD68^(+)CD206^(+)阳性表达率升高(P<0.05),外周血内F4/80^(+)CD86^(+)标记细胞比例也降低,F4/80^(+)CD206^(+)标记细胞比例则升高(P<0.05)。结论:DMF能够提高ITP小鼠PLT数量,减少脾脏与骨髓内�Objective:To explore the effect of dimethyl fumarate(DMF)on primary immune thrombocytopenia(ITP)by regulating the polarization of macrophages.Methods:The BALB/c mice were divided into control group,ITP group,DMF low-dose group and DMF high-dose group,each with 15 mice.Except for the control group,the other three groups of mice were all constructed with ITP models.Mice in low-dose DMF group and high-dose DMF group were given 10 mg/kg and 20 mg/kg DMF by gavage,once a day for 14 consecutive days.The automatic blood cell analyzer was used to detect the levels of peripheral blood platelets(PLT),red blood cells(RBC),white blood cells(WBC)and hemoglobin(Hb)in mice;ELISA method was used to detect the levels of serum IFN-γ,IL-2,IL-4,IL-10,IL-17 and TGF-β1 in mice.Electronic balance was used to weight mouse body weight,spleen and thymus,and organ index was calculated;HE staining was used to observe the number of megakaryocytes in mouse spleen tissue and bone marrow tissues;Immunofluorescence staining was used to detect the polarization of macrophages in mouse spleen tissues;Flow cytometry was used to determine the polarization of macrophages in the peripheral blood of mice.Results:After the modeling started,the number of peripheral blood platelets of mice decreased significantly compared with that of control mice(P<0.05),indicating that the modeling was successful.After modeling,compared with control group,the PLT,RBC and Hb of ITP group were decreased,WBC was increased(P<0.05),the serum levels of IFN-γ,IL-2 and IL-17 were increased,and TGF-β1,IL-4 and IL-10 were all decreased(P<0.05),the spleen index was increased(P<0.05),the number of megakaryocytes in spleen and bone marrow were increased(P<0.05),the positive expression rate of M 1 macrophage marker CD680^(+)CD860^(+)in spleen tissue was increased,and the positive expression rate of M_(2) macrophage marker CD680^(+)CD2060^(+)was decreased(P<0.05),the proportion of F_(4)/800^(+)CD860^(+)labeled cells in peripheral blood was increased,and the proportion of F_(4)/800^

关 键 词：原发免疫性血小板减少症 富马酸二甲酯 血小板 巨噬细胞 

分 类 号：R558[医药卫生—血液循环系统疾病]