正清风痛宁片与甲氨蝶呤对胶原诱导性关节炎大鼠血清骨保护素/核因子κB受体活化因子配体及白细胞介素-17的影响

[Effects of zhengqing fengtongning tablet and methotrexate on the serum OPG/RANKL and IL-17 of collagen-induced arthritis rats].

作者信息

Ding Cong-Zhu, Yao Yao, Fang Yun, Sun Ling-Yun, Wang Yue

机构信息

Department of Rheumatology and Immunology, Affiliated Drum Tower Clinical Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing (210008), China.

出版信息

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013 Feb;33(2):256-60.

PMID:23646485

Abstract

OBJECTIVE

To study the effects of Zhengqing Fengtongning Tablet (ZFT) and methotrexate (MTX) on the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), and interleukin 17 (IL-17) in collagen-induced arthritis (CIA) rats, thus addressing their bone protection.

METHODS

The CIA rat model was established by intradermally injecting type II collagen emulsion from the rats' back and tail. Totally 28 successfully modeled rats [with the arthritis index (AI) more than 2] were randomly divided into the model group, the Chinese medicine (CM) treatment group, the MTX group, and the ZFT + MTX treatment group, 7 rats in each group. Another 7 rats were recruited as the normal control group. Rats were administered from the 7th day of modeling. Rats in the MTX group were treated with MTX at 3.8 mg/kg once a week. Those in the CM group were treated with ZFT at the daily dose of 130 mg/kg, once a day. Those in the ZFT + MTX treatment group were treated with both MTX (at 3.8 mg/kg once a week) and ZFT (at the daily dose of 130 mg/kg, once a day). Those in the model group and the normal control group were administered with normal saline of the equal volume by gastrogavage. All the intervention lasted for 26 days. The destruction of joints in the four limbs were observed using X-ray. The AI was recorded. The expression levels of serum OPG, RANKL, and IL-17 were detected at the end of the experiment.

RESULTS

During the whole process, all rats except those in the model group were in a good condition. On the 21st day of modeling the AI of all rats reached the peak, but it decreased after treatment. Compared with the model group, the AI decreased in the CM treatment group, the MTX group, and the ZFT + MTX treatment group with statistical difference (P < 0.05). Compared with the model group, the OPG increased and RANKL decreased in the MTX group; the OPG and OPG/RANKL increased in the CM treatment group; the OPG, RANKL, and OPG/RANKL increased, and IL-17 decreased in the ZFT + MTX treatment group, all showing statistical difference (P < 0.05). Compared with the MTX and the ZFT + MTX treatment group, OPG/RANKL increased and IL-17 decreased in the ZFT + MTX treatment group (both P < 0.05).

CONCLUSION

ZFT + MTX could synergistically elevate peripheral OPG/RANKL and down-regulate IL-17 in CIA model rats.

摘要

目的

研究正清风痛宁片（ZFT）和甲氨蝶呤（MTX）对胶原诱导性关节炎（CIA）大鼠骨保护素（OPG）、核因子κB受体活化因子配体（RANKL）及白细胞介素17（IL-17）表达的影响，以探讨其对骨的保护作用。

方法

通过大鼠背部及尾部皮内注射Ⅱ型胶原乳剂建立CIA大鼠模型。将28只造模成功[关节炎指数（AI）大于2]的大鼠随机分为模型组、中药治疗组、MTX组和ZFT+MTX治疗组，每组7只。另取7只大鼠作为正常对照组。从造模第7天开始给药。MTX组大鼠每周一次给予MTX 3.8 mg/kg；中药组大鼠每日一次给予ZFT 130 mg/kg；ZFT+MTX治疗组大鼠同时给予MTX（每周一次，3.8 mg/kg）和ZFT（每日一次，130 mg/kg）；模型组和正常对照组大鼠经灌胃给予等体积生理盐水。所有干预持续26天。采用X线观察四肢关节破坏情况，记录AI。实验结束时检测血清OPG、RANKL及IL-17表达水平。

结果

整个过程中，除模型组外所有大鼠状态良好。造模第21天所有大鼠AI达峰值，治疗后降低。与模型组比较，中药治疗组、MTX组及ZFT+MTX治疗组AI降低，差异有统计学意义（P<0.05）。与模型组比较，MTX组OPG升高、RANKL降低；中药治疗组OPG及OPG/RANKL升高；ZFT+MTX治疗组OPG、RANKL及OPG/RANKL升高，IL-17降低，差异均有统计学意义（P<0.05）。与MTX组和ZFT+MTX治疗组比较，ZFT+MTX治疗组OPG/RANKL升高，IL-17降低（均P<0.05）。