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

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

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。

BACKGROUND：At present, spleen tyrosine kinase is the new target of studying and treating rheumatoid arthritis. OBJECTIVE：To study the influence of smal molecule tyrosine kinase inhibitor HL131078 on the inflammatory cel infiltration and cartilage destruction of the knee joint of mice with col agen-induced arthritis. METHODS：Forty DBA/1 mice were randomly and evenly divided into blank, model, positive and experimental groups. Col agen 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 col agen-induced arthritis. At 2 weeks after the the first immunization with CII, the mice in the positive group were intragastrical y given R406 （10 mg/kg）, once a day, for 28 consecutive days. The mice in the experimental group were intragastrical y 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 cel infiltration in the knee joints was obviously reduced, which was close to that in the positive group. The results demonstrate that the smal molecule tyrosine kinase inhibitor HL131078 can effectively reduce inflammatory cel infiltration and cartilage destruction in＆amp;nbsp;the knee joints of mice with col agen-induced arthritis.