巴多昔芬治疗小鼠胶原诱导性关节炎的疗效及对滑膜成纤维细胞的影响  

Efficacy of bazedoxifene in the treatment of collagen-induced arthritis(CIA)in mice and its effect on fibroblast-like synoviocytes

作　　者：张莹 代春燕 田静[3] 田吉来 ZHANG Ying;DAI Chunyan;TIAN Jing;TIAN Jilai(Department of Rheumatology and Immunology,Nanjing Drum Towel Hospital,The Affiliated Hospital of Medical School,Nanjing University,Nanjing 210008,China;Department of Endocrinology and Nephrology,Xiajin People′s Hospital,Dezhou 253200,China;Department of Biochemistry and Molecular Biology,School of Medicine&Holistic Integrative Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]南京大学医学院附属鼓楼医院风湿免疫科,江苏南京210008 [2]夏津县人民医院内分泌肾病科,山东德州253200 [3]南京中医药大学医学院·整合医学学院生物化学与分子生物学系,江苏南京210023

出　　处：《药学研究》2023年第9期648-653,共6页Journal of Pharmaceutical Research

基　　金：国家自然科学基金(No.82001720)。

摘　　要：目的探究巴多昔芬(BAZ)对小鼠胶原诱导性关节炎的治疗作用和对MH7A滑膜成纤维细胞增殖、侵袭和迁移的影响。方法采用牛Ⅱ型胶原诱导(CIA)DBA/1小鼠类风湿性关节炎模型,通过关节炎评分、测量后足厚度等方法评价BAZ对小鼠关节炎的治疗作用,采用苏木精伊红和番固红绿染色检测小鼠关节病理变化,采用micro-CT进一步验证BAZ对关节骨破坏的影响。采用CCK-8法、平板克隆实验、细胞划痕实验和Transwell小室的方法考察BAZ对MH7A细胞的存活、增殖、迁移和侵袭的影响。结果BAZ能显著地降低关节炎评分,减轻后足肿胀;病理切片显示,BAZ能显著减少滑膜炎、血管翳、软骨侵袭和骨质破坏;BAZ与gp130抑制剂SC144均可有效抑制MH7A细胞的增殖,降低MH7A细胞迁移和侵袭能力。结论BAZ对小鼠胶原诱导性关节炎有较好治疗作用,其作用可能与抑制滑膜成纤维细胞增殖、侵袭和迁移有关。Objective To explore the efficacy of bazedoxifene(BAZ)in the treatment of collagen-induced arthritis(CIA)in mice,and its effects on proliferation,invasion and migration of fibroblast-like synoviocytes MH7A.Methods Bovine typeⅡcollagen induced rheumatoid arthritis(CIA)mice were used.The efficacy of BAZ on CIA mice was evaluated by arthritis score and hind foot thickness.The pathological changes of mice joints were calculated on hematoxylin eosin and safranine o and fast green staining.The effects of BAZ on the survival,proliferation,migration and invasion of MH7A cells were investigated by CCK-8 assay,cloning formation,cell wound healing,and Transwell chamber,respectively.Results BAZ can significantly reduce the arthritis score and reduce the swelling of hind foot.Pathological sections showed that BAZ could significantly reduce synovitis,pannus,cartilage invasion and bone destruction.Both BAZ and gp130 inhibitor SC144 can effectively inhibit the proliferation of MH7A cells and reduce the migration and invasion ability of MH7A cells.Conclusion BAZ might have therapeutic effects on CIA mice by inhibiting synovial cell proliferation,invasion and migration.

关 键 词：巴多昔芬 白细胞介素-6/糖蛋白130 类风湿性关节炎 滑膜成纤维细胞 

分 类 号：R965[医药卫生—药理学]