艾拉莫德治疗博来霉素诱导硬皮病小鼠的实验研究  

Effects of iguratimod on mouse with systemic scleroderma induced by bleomycin

作　　者：姚根宏[1] 米日班姑·阿力甫 聂敏 马晓蕾[1] 陈智勇[1,2] Yao Genhong;Miribangu·Alipu;Nie Min;Ma Xiaolei;Chen Zhiyong(Department of Rheumatology and Immunology,the Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing 210008,China;Department of Rheumatology and Immunology,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,Shanghai 200233,China)

机构地区：[1]南京大学医学院附属鼓楼医院风湿免疫科,南京210008 [2]上海交通大学医学院附属第六人民医院风湿免疫科,上海200233

出　　处：《国际免疫学杂志》2022年第3期274-277,共4页International Journal of Immunology

基　　金：中华国际医学交流基金会类风湿关节炎专项基金(Z-2018-40)。

摘　　要：目的研究艾拉莫德(iguratimod,IGU)治疗硬皮病小鼠的疗效和机制,为IGU治疗临床硬皮病患者提供理论和实验依据。方法采用100μg/0.1 mL的博来霉素每天注射于C57BL/6小鼠背部皮肤4周,建立硬皮病小鼠模型。硬皮病小鼠随机分为IGU治疗组和对照组,每组5只。治疗组小鼠每日灌胃IGU 1次(50 mg/kg/d,250μL),对照组以等量生理盐水处理。采用苏木精-伊红染色法(hematoxylin-eosin staining,HE)和masson染色法观察小鼠皮肤组织病理,酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测小鼠血浆中白细胞介素(interleukin,IL)-1β、IL-18及β-干扰素(interferon-β,IFN-β)的表达。结果与对照组相比,IGU治疗组小鼠皮肤硬化现象明显改善,皮肤胶原束增厚和胶原纤维沉积情况明显减轻。IGU治疗组小鼠外周血中炎症因子IL-1β,IL-18和IFN-β较对照组显著降低,差异具有统计学意义[(20.86±8.35)pg/mL比(139.10±48.79)pg/mL,(0.81±0.06)ng/mL比(3.39±0.44)ng/mL,(712.60±20.02)pg/mL比(836.50±36.18)pg/mL,t值分别为2.39、5.79、2.99,P值均<0.05]。结论IGU治疗硬皮病小鼠具有一定的效果,其机制可能是通过抑制炎症因子进而改善皮肤损伤。Objective To explore the effects and mechanism of iguratimod(IGU)on mice with systemic scleroderma induced by bleomycin,and to provide theoretical and experimental evidences for clinic application of IGU on patients with systemic scleroderma.Methods The dorsal area of C57BL/6 mice was injected with bleomycin(100μg/0.1 mL/d)for 4 weeks to establish scleroderma mice model.The mice with systemic scleroderma were randomly divided into control group and IGU treatment group with 5 mice in each group.The treatment group were administered intragastrically of IGU once a day(50 mg/kg/d,250μL).The control group was treated with the same volume of normal saline.Hematoxylin eosin staining(HE)and masson staining were used to observe the histopathology of mouse skin.The interleukin(IL)-1,IL-18,and interferon-β(IFN-β)in the serum were detected by enzyme linked immunosorbent assay(ELISA).Results Compared with the control group,the skin sclerosis of mice in IGU treatment group was significantly improved,the thickening of skin collagen bundle and the deposition of collagen fibers were significantly reduced.Inflammatory factor IL-1β,IL-8,and IFN-βin peripheral blood of IGU treatment group were significantly reduced compared with the control group[(20.9±8.3)pg/mL vs(139.1±48.8)pg/mL,(0.81±0.06)ng/mL vs(3.39±0.44)ng/mL,(712.60±20.02)pg/mL vs(836.50±36.18)pg/mL,t values were 2.39,5.79 and 2.99 respectively,all P values<0.05].Conclusion IGU has a certain effect on ameliorated systemic scleroderma in mice,and its mechanism may be through inhibiting inflammatory factors and contributing to alleviating skin injury.

关 键 词：艾拉莫德 硬皮病 炎症因子 

分 类 号：R593.25[医药卫生—内科学]