乌梢蛇Ⅱ型胶原对关节炎大鼠免疫功能的影响

Effectiveness of type Ⅱ collagen from Zaocys dhumnades （Cantor） on the immune functions of rats with collagen-induced arthritis

目的研究乌梢蛇Ⅱ型胶原对关节炎大鼠的免疫调节作用，以了解乌梢蛇治疗类风湿关节炎（RA）的机制。方法关节炎大鼠随机分成3组，即乌梢蛇Ⅱ型胶原组、牛Ⅱ型胶原组和关节炎对照组，另设健康对照组，每组7只，乌梢蛇Ⅱ型胶原组和牛Ⅱ型胶原组分别灌胃乌梢蛇Ⅱ型胶溶液1ml（Ⅱ型胶原15mg／kg）和牛Ⅱ型胶溶液1ml（Ⅱ型胶原15mg／kg），另两组灌胃不含胶原的胶原稀释液1ml，每日1次，连续15d后，取大鼠外周血测抗Ⅱ型胶原抗体、淋巴细胞亚群、肿瘤坏死因子（TNF）-01、白细胞介素（IL）-10、IL-1和IL-4水平。结果关节炎对照组：抗Ⅱ型胶原抗体、TNF-α水平和CD4^＋T／CD8^＋比值与健康对照组相比明显升高（P〈0．05），IL-10水平明显下降（P〈0．01）；乌梢蛇Ⅱ型胶原组和牛Ⅱ型胶原组：TNF-α水平和CD4^＋T／CD8^＋比值与关节炎对照组相比明显下降（P〈0．05），与健康对照组比较差异无统计学意义（P〉0．05），抗Ⅱ型胶原抗体滴度较关节炎对照组下降（P〈0．05），与健康对照组差异有统计学意义（P〈0．01），IL-10水平较关节炎对照组升高（P〈0．01），与健康对照组差异有统计学意义（P〈0．05），口服Ⅱ型胶原两组间各项免疫指标比较差异均无统计学意义（P〈0．05）；外周血IL-1和IL-4水平，4组差异无统计学意义（P〉0．05）。结论乌梢蛇Ⅱ型胶原与牛Ⅱ型胶原具有相同的免疫调节作用，两者能减低关节炎大鼠外周血TNF-α水平、抗Ⅱ型胶原抗体滴度和CD4^＋T／CD8^＋比值，提高IL^-10水平的作用，推测乌梢蛇Ⅱ型胶原可能是乌梢蛇治疗RA的活性药理成分。

Objective To study the effeet of type Ⅱ collagen （C Ⅱ ） from Zaoeys dummies （Cantor） on the immune functions of rats with collagen-induced arthritis and to understand the mechanisms of RA treated with Zaocys dhumnades （Cantor）. Methods The rats with collagen-induced arthritis were randomly divided into three group： C Ⅱ from Zaocys dhumnades, bovine C Ⅱ and arthritis control group, a normal control group was set up, too. Every group had 7 rats. The C Ⅱ from Zaocys dhumnades and the bovine C Ⅱ group were fed with C Ⅱ from Zaocys dhumnades （ 15 mg/kg） and bovine C Ⅱ （ 15 mg/kg） per day respectivelyfor 15 days. The CD4/CD8 subset ratio, serum levels of anti-C Ⅱ antibody, TNF-α, IL-10, IL-1 and IL-4 in .rats were measured. Results In the arthritis group, CD4/CD8 subset ratio （P〈0.05） and serum levels of type Ⅱ collagen antibody （P〈0.01） and TNF-α （P〈0.01） were significant increased and IL-10 （P〈0.01） was significantly decreased. In the C Ⅱ from Zaoeys dhumnades and bovine C Ⅱ group, CD4/CD8 subset ratio （P〈0.05） and the level of TNF-α （P〈0.01） were significantly decreased compared with the arthritis group, and had no difference compared with the normal group. The level of anti-C Ⅱ antibody was declined significantly compared with the arthritis group （P〈0.05） and had statistical difference with the normal group （P〈0.01）. The level of IL-10 was significantly increased（P〈0.01 ）, but lower than the normal group（P〈 0.05）. There was no statistical difference in the level of IL-1 and IL-4 in all four groups. Conclusion C Ⅱ from Zaocys dhum-nades （Cantor） is as effective as bovine C Ⅱ in modifying the immune functions of collagen-induced arth-ritis in rats. They can decrease the level of anti-C Ⅱ antibody, the level of TNF-α, CD4/CD8 subset ratio and increase the level of IL-10 in the peripheral blood of rats with collagen-induced arthritis. C Ⅱ from Zaocys dhumnades may be one of the important pharmacological active components that have the potential in treating rheumatoid arthritis.