中国组织工程研究

中国组织工程研究 ›› 2015, Vol. 19 ›› Issue (24): 3783-3787.doi: 10.3969/j.issn.2095-4344.2015.24.003

• 软骨组织构建 cartilage tissue construction • 上一篇    下一篇

酪氨酸激酶抑制化合物干预胶原诱导关节炎模型炎性细胞浸润及软骨破坏

刘  韦1，张  勇1，耿德春1，黄立新1，李  剑2   

  1. 1苏州大学附属第一医院骨科，江苏省苏州市  215006； 2华东理工大学药学院，上海市  200237
  • 出版日期:2015-06-11 发布日期:2015-06-11
  • 通讯作者: 李剑，教授，华东理工大学药学院，上海市 200237
  • 作者简介:刘韦，男，1988年生，江苏省淮安市人，汉族，苏州大学在读硕士，主要从事关节外科的研究。
  • 基金资助:

    国家自然科学基金项目(81472077，81372018)；江苏省卫生厅项目(H201417)；苏州市科技计划项目(SYS201321)

Intervention of inflammatory cell infiltration and cartilage destruction of the knee joints in mouse models of collagen-induced arthritis by small molecule tyrosine kinase inhibitors 

Liu Wei1, Zhang Yong1, Geng De-chun1, Huang Li-xin1, Li Jian2   

  1. 1Department of Orthopedics, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China; 2College of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
  • Online:2015-06-11 Published:2015-06-11
  • Contact: Li Jian, Professor, College of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
  • About author:Liu Wei, Studying for Master’s degree, Department of Orthopedics, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
  • Supported by:

     the National Natural Science Foundation of China No. 81472077, 81372018; a grant from the Program of Jiangsu Provincial Health Department of China, No. H201417; a grant from the Science and Technology Program of Suzhou City of China, No. SYS201321

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摘要：

背景：脾酪氨酸激酶是目前研究治疗类风湿关节炎的新靶点。
目的：研究小分子酪氨酸激酶抑制化合物HL131078对胶原诱导型关节炎小鼠膝关节炎性细胞浸润、软骨破坏的影响。
方法：将40只DBA/1系小鼠随机等分为空白组、模型组、阳性组和实验组。后3组小鼠尾部注射CⅡ型胶原溶液与弗氏完全佐剂(含结核杆菌)建立胶原诱导型关节炎小鼠模型。第1次免疫注射2周后，阳性组小鼠灌胃10 mg/kg R406，1次/d，连续28 d；实验组灌胃10 mg/kg小分子化合物HL131078，1次/d，连续28 d。
结果与结论：与模型组相比，实验组和阳性组小鼠平均关节炎指数分别于第29和26天时开始下降，且实验组小鼠膝关节的软骨破坏情况明显减轻，仍维持较好的完整性，膝关节腔内炎性细胞的浸润明显减轻，与阳性药物R406效果接近。说明小分子酪氨酸激酶抑制化合物HL131078可以有效缓解胶原诱导型关节炎小鼠膝关节腔内炎性细胞的浸润，减轻软骨破坏情况。

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 组织构建, 骨组织工程, 胶原诱导, 动物模型, 类风湿关节炎, 小分子酪氨酸激酶抑制剂, HL131078, R406, 国家自然科学基金

Abstract:

BACKGROUND: At present, spleen tyrosine kinase is the new target of studying and treating rheumatoid arthritis.
OBJECTIVE: To study the influence of small molecule tyrosine kinase inhibitor HL131078 on the inflammatory cell infiltration and cartilage destruction of the knee joint of mice with collagen-induced arthritis.
METHODS: Forty DBA/1 mice were randomly and evenly divided into blank, model, positive and experimental groups. Collagen type II (CII) solution and Freund’s complete adjuvant (including mycobacterium tuberculosis) were injected into the mice of the latter three groups through the tail to establish mouse models of collagen-induced arthritis. At 2 weeks after the the first immunization with CII, the mice in the positive group were intragastrically given R406 (10 mg/kg), once a day, for 28 consecutive days. The mice in the experimental group were intragastrically given HL131078 (10 mg/kg), once per day, for 28 consecutive days.
RESULTS AND CONCLUSION: Compared with the model group, the mean arthritis indexes of mice in the experimental and positive groups started to decline at 29 and 26 days. In the experimental group, the cartilage destruction of mouse knee joint was obviously reduced and the inflammatory cell infiltration in the knee joints was obviously reduced, which was close to that in the positive group. The results demonstrate that the small molecule tyrosine kinase inhibitor HL131078 can effectively reduce inflammatory cell infiltration and cartilage destruction in the knee joints of mice with collagen-induced arthritis.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Arthritis, Osteoarthritis, Knee, Protein-Tyrosine Kinases, Cartilage

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