淫羊藿苷对牛Ⅱ型胶原诱导型关节炎小鼠IL-17/RANKL轴的影响

Effects of Icariin on IL-17-associated RANKL of Type Ⅱ Collagen-induced Arthritis in Mice

目的初步观察淫羊藿苷(Icariin,ICA)对牛Ⅱ型胶原诱导型关节炎(typeⅡcollagen-induced arthritis,CIA)DBA/1小鼠IL-17/RANKL的调节作用。方法除正常对照组(N组,灌胃给予生理盐水3 ml·kg-1·d-1)外以牛Ⅱ型胶原和弗氏不完全佐剂注射诱导DBA/1小鼠关节炎模型;将32只建模成功(关节炎指数评分≥4分)DBA/1小鼠随机分为模型对照组(Con组,灌胃给予生理盐水3 ml·kg-1·d-1)、甲氨喋呤组(MTX组,灌胃给予每周MTX 1.5 mg·kg-1)、淫羊藿低剂量组(IL组,灌胃给予ICA 5 mg·kg-1·d-1)和淫羊藿苷高剂量组(IH组,灌胃给予ICA 20 mg·kg-1·d-1),每组8只,连续干预15 d,并于第3,7,11,15 d记录各组小鼠关节炎指数评分值。干预结束后检测各组关节炎小鼠血清白介素-17(IL-17)、白介素-23(IL-23)、NF-KB配体的受体或激活因子(RANKL)和抗酒石酸酸性磷酸酶(Tracp)含量。结果第2次免疫后1周左右,Con组足趾肿胀明显,关节炎指数评分明显高于N组,差异具有显著性(P<0.01);干预15 d后,与N组比较,Con组IL-23、Tracp、IL-17和RANKL浓度升高,在IL-23和Tracp水平上差异有统计学意义(P<0.05),而IL-17和RANKL两个指标差异无统计学意义(P>0.05);与Con组比较,MTX组血清IL-23水平降低(P<0.05),IL组IL-23和RANKL含量降低(P<0.01,P<0.05),IH组IL-17、IL-23、RANKL和Tracp水平均显著降低(P<0.01);IH组与IL组相比,RANKL和Tracp均明显降低,差异具有统计学意义(P<0.01,P<0.05)。结论淫羊藿苷能改善CIA DBA/1小鼠足趾局部肿胀程度,下调血清IL-23和IL-17、RANKL和Tracp水平,具有调节骨免疫系统的潜能。

Objective To observe the effects of Icariin on regulating IL - 17 - associated RANKL of type Ⅱ collagen - induced arthritis in DBA/1 mice. Methods Except the normal group（ fed with normal saline 3 ml · kg^-1·d^-1 ） , all mice were established type Ⅱ collagen - induced arthritis model. 32 arthritis mice with arthritis score at 4 at least were divided into control group （ fed with normal saline 3 ml·kg^-1·d^-1 ） ,MTT group（fed with methotrexate 1.5 mg · kg^-1 · week^-1 ） ,high - dose [CA group（fed with Icariin 20 mg · kg^- 1· d ^- 1 ） and low - dose ICA group （ fed with Icariin 5 mg· kg^- 1 · d^ - 1 ）, recording arthritis score of each group on the 3rd,7th,llth and 15th days. The levels of serum IL - 17,1L -23,RANKL and Tracp were detected by enzyme -linked immunosorbent assay after intervention for 14 days. Results Compared with normal group, the arthritis index of control group was significantly higher when one week after the second immunization （P 〈 0.01 ）. After being intervened for 15 days, control group had a higher level of IL - 17 ,IL - 23 ,RANKL and Tracp than that of normal group ; compared with control group, MTX could reduce the arthritis score and also down- regulate the serum IL- 23 level significantly（ P 〈0.05） ;Icariin could also improve the arthritis score（ P 〈 0.05 ） ,lowdose icariin can significantly inhibit the expression of IL- 23 and RANKL in serum（ P 〈 0.05 ）, and highdose icariin had a significant effect in reducing the contents of IL- 17 ,IL- 23, RAN KL and Traep （P 〈 0.05 ）. Con- clusion Ieariin can improve CIA DBA/1 mice local paw swelling and reduce serum levels of IL - 17 .IL -23 ,RANKL and Tracp, which may be its mechanism in regulating osteoimmune system.