| 韩新爱,何 娟,宋 睿,张晓明,接红宇.AZD5069通过抑制中性粒细胞迁移治疗类风湿关节炎的机制研究[J].,2020,(13):2406-2410 |
| AZD5069通过抑制中性粒细胞迁移治疗类风湿关节炎的机制研究 |
| Mechanism of AZD5069 in the Treatment of Rheumatoid Arthritis by Inhibiting Neutrophil Migration |
| 投稿时间：2020-02-05 修订日期：2020-02-28 |
| DOI：10.13241/j.cnki.pmb.2020.13.002 |
| 中文关键词: AZD5069 小鼠 类风湿关节炎 中性粒细胞迁移 |
| 英文关键词: AZD5069 Mice Rheumatoid arthritis Neutrophil migration |
| 基金项目:国家自然科学基金项目（31600732）；广州市天河区科技计划项目（201704KW0） |
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| 中文摘要: |
| 摘要 目的：探讨 CXCR2 拮抗剂 AZD5069 能否通过抑制中性粒细胞迁移治疗类风湿关节炎（RA）。方法：将45只雄性 DBA/1J 小鼠随机分为对照组（n=15）、模型组（n=15）、AZD5069 组（n=15）；除对照组外，其余两组均给予牛Ⅱ型胶原蛋白+弗氏佐剂建立胶原诱导型关节炎（CIA)模型。观察记录小鼠关节炎评分。二次免疫后第二天给与药物治疗，治疗 3 周后处死小鼠检测关节病理、中性粒细胞浸润、外周血炎症因子等指标。结果：与对照组相比，模型组小鼠关节炎发病率明显升高（P＜0.05）；与模型组相比，AZD5069 组小鼠关节炎发病率明显降低（P＜0.05）。与对照组相比，模型组小鼠关节炎评分明显升高（P＜0.05）；与模型相比，AZD5069 组小鼠关节炎评分明显降低（P＜0.05）。对照组小鼠踝关节间隙正常，滑膜无增生，无炎症细胞浸润，软骨面光滑无破坏；模型组小鼠踝关节间隙狭窄，滑膜增生明显，可见大量炎症细胞浸润，软骨侵蚀破坏；与模型组相比，AZD5069 组小鼠踝关节间隙未见明显狭窄，滑膜未见明显增生，炎症细胞浸润明显减轻，软骨未见明显破坏。与对照组相比，模型组小鼠血清中炎症因子 TNF-α、IL-1β的水平明显升高（P＜0.05）；与模型组相比，AZD5069 组小鼠血清中炎症因子 TNF-α、IL-1β 的水平明显降低（P＜0.05）。与对照组相比，模型组小鼠踝关节中性粒细胞明显增多，可见大量中性粒细胞浸润；与模型组相比，AZD5069组小鼠踝关节中性粒细胞明显减少，中性粒细胞浸润情况明显减轻。结论：CXCR2 拮抗剂 AZD5069 可通过抑制中性粒细胞迁移治疗类风湿关节炎，为开发新型治疗 RA 药物提供理论基础。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate whether CXCR2 antagonist AZD5069 can treat rheumatoid arthritis (RA) by inhibiting neutrophil migration. Methods: 45 Male DBA/1J mice were randomly divided into a control group(n=15), model(CIA) group(n=15), AZD5069 group(n=15). Except for the control group, the other two groups were given bovine type II collagen and Freund's adjuvant to establish collagen-induced arthritis (CIA) model. The arthritis scores of mice were observed and recorded. Drug treatment was given the day after the secondary immunization, the mice were sacrificed after 3 weeks of treatment to measure joint pathology, neutrophil infiltration and peripheral blood inflammatory factors. Results: Compared with the control group, the incidence rate of arthritis in the CIA group increased significantly(P<0.05), and the incidence rate of arthritis in AZD5069 group was significantly lower than that in the model group (P<0.05). Compared with the control group, the arthritis score in the CIA group was significantly higher(P<0.05); compared with the CIA group, the arthritis score in the azd5069 group was significantly lower(P<0.05). In the control group, the ankle joint space was normal, there was no proliferation of synovium, no infiltration of inflammatory cells, and the cartilage surface was smooth and undamaged; in the CIA group, the ankle joint space was narrow, with obvious proliferation of synovium, with a large number of inflammatory cells infiltration and cartilage erosion; compared with the CIA group, azd5069 group showed no obvious stenosis of ankle joint space, no obvious hyperplasia of synovium, inflammatory cell infiltration was significantly reduced, cartilage was not damaged. Compared with the control group, the serum levels of TNF-α and IL-1β in the CIA group were significantly higher(P<0.05); compared with the CIA group, the serum levels of TNF-α and IL-1β in the azd5069 group were significantly lower(P<0.05). Compared with the control group, the number of neutrophils in the CIA group was significantly increased, and a large number of neutrophils infiltration could be seen; compared with the CIA group, the number of neutrophils in the azd5069 group was significantly reduced, and the infiltration of neutrophils was significantly reduced. Conclusion: CXCR2 antagonist AZD5069 can treat rheumatoid arthritis by inhibiting neutrophil migration and provide a theoretical basis for developing new drugs for treating RA. |
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