HLA-DRB1结合性Ⅱ型胶原多肽抑制胶原性关节炎的实验研究

HLA-DRB1 binding CⅡ263-272 peptide inhibits collagen-induced arthritis

目的：研究替换CⅡ263-272序列中的268～270位氨基酸的变构肽sub268-270对胶原性关节炎（CIA）的抑制作用。方法：使用牛CⅡ在Lewis大鼠诱发CIA。以CⅡ变构肽sub268-270 90μg静脉注射，每周1次治疗CIA；设置无关肽对照和空白对照组。从关节炎症积分、放射学积分和病理学积分来评价变构肽疗效。结果：变构肽、无关肽及空白对照组关节炎症积分分别为5．60±1．24、11．20±1．21和11．80±1．22，变构肽可明显抑制CIA关节炎症（P〈0．01）。变构肽组的放射学积分（1．32±0．49）明显低于无关肽组（2．63±0．51）和空白对照组（2．69±0．53）（P〈0．01）。此外，变构肽组的病理学积分（1．37±0．53）也显著低于无关肽组（2．94±0．63）和空白对照组（3．06±0．65）（P〈0．01）。结论：CⅡ变构肽sub268-270可以明显抑制胶原性关节炎的关节炎症、病理损伤及骨破坏程度。

Objective：To study the inhibition of collagen-induced arthritis by an altered C Ⅱ 263-272 peptide （sub268-270） with three consecutive substitutions of TCR-contacting residues. Methods： Arthritis was induced by bovine collagen type Ⅱ. The altered peptide sub268-270 was given intravenously with a dose of 90 μg once a week. Peptide control and blank control were treated with similar approaches. The therapeutic effect of the altered peptide was evaluated by arthritis score index, radiological score and pathological score. Results ：The arthritis score of rats treated with altered peptide, control peptide and blank control were 5.60 ± 1.24, 11.20 ± 1.21 and 11.80 ± 1.22 respectively（ P 〈 0. 01 ）, implying that the altered C Ⅱ peptide could decrease arthritis score of CIA. The radiological score of rats treated with altered peptide, control peptide and blank control were 1.32 ± 0. 49, 2. 63 ± 0. 51 and 2. 69 ± 0. 53 （P 〈0. 01 ） , showing that the altered C Ⅱ peptide could decrease CIA radiological lesions. The pathological score of rats treated with altered peptide, control peptide and blank control were 1.37 ± 0. 53, 2. 94 ± 0. 63 and 3. 06±0. 65 （ P 〈 0. 01 ）, suggesting that the altered C Ⅱ peptide could retard CIA pathological injury. Concluslon：Altered C Ⅱ peptide sub268-270 could effectively ameliorate arthritis in CIA.