Mtb诱导的佐剂性关节炎大鼠滑膜病变的蛋白质组学研究

Proteomics study of synovial lesions in rats with Mtb-induced rheumatoid arthritis

目的通过比较Mtb诱导的佐剂性关节炎大鼠和正常大鼠关节滑膜组织蛋白质谱的差异,探讨类风湿性关节炎可能的发病机制,寻找类风湿性关节炎致病相关蛋白。方法建立Mtb诱导的佐剂性关节炎大鼠模型。采用双向凝胶电泳的蛋白质组学技术比较Mtb诱导的佐剂性关节炎大鼠和正常大鼠关节滑膜组织蛋白质谱的差异;采用Western blot技术和荧光定量PCR技术验证其中2种差异蛋白表达情况。结果建立了佐剂性关节炎模型组及正常组滑膜组织双向凝胶电泳图谱,获得变化趋势2倍以上的蛋白质点8个,其中模型组相对于空白对照组下调蛋白4个,模型组相对于空白对照组上调蛋白4个。Western blot方法和荧光定量方法对其中2种蛋白进行验证,结果与蛋白质组学结果一致。结论类风湿关节炎滑膜病变是一个多种蛋白质参与的复杂过程,这些表达差异蛋白质可能参与了类风湿性关节炎的进展。

Objective To characterize the proteomic profiles of joint synovial tissue in normal rats and rats with rheumatoid arthritis （RA） and identify the proteins related with the occurrence of RA to explore the pathogenesis of RA. Methods SD rat models of RA were established using Mtb （heat-killed Mycobacterium tuberculosis H37Ra）. Two-dimensional gel electrophoresis proteomics technology was employed to analyze the difference in synovial tissue protein profiles between RA model rats and normal rats, and two of the differentially expressed proteins were verified with Western blotting and fluorescence quantitative PCR. Results Comparison of the two-dimensional gel electrophoresis patterns from the model rats and normal rats showed 4 up-regulated and 4 down-regulated proteins by 2 folds in the RA model rats. Western blotting and fluorescent quantitative PCR of 2 of the 8 proteins yielded consistent results with those by proteomics analysis. Conclusion Arthritis synovial lesions in RA represent very complex pathological processes involving a variety of proteins, and these differentially expressed proteins may contribute to the progression of RA.