Cox-2抑制与肌腱愈合早期和中期炎症细胞群的组成
Cox-2 inhibition and the composition of inflammatory cell populations during early and mid-time tendon healing.
作者信息
Blomgran Parmis, Blomgran Robert, Ernerudh Jan, Aspenberg Per
机构信息
Department of Clinical and Experimental Medicine, Linkoping University, Sweden.
Department of Medical Microbiology, Linkoping University, Sweden.
出版信息
Muscles Ligaments Tendons J. 2017 Sep 18;7(2):223-229. doi: 10.11138/mltj/2017.7.2.223. eCollection 2017 Apr-Jun.
BACKGROUND
During early tendon healing, the cells within the regenerating tissue are, to a large part, inflammatory leukocytes (CD45). In a rat Achilles tendon healing model, the inflammation resolves between 5 and 10 days. In the same model, Cox inhibitors (NSAIDs) impair healing when given during the first 5 days, but have a positive effect if given later. We tested the hypothesis that a Cox inhibitor would exert these effects by influencing inflammation, and thereby the composition of the inflammatory cell subpopulations.
METHODS
Achilles tendon transection was performed in 44 animals. Animals were randomized to either parecoxib or saline injections. Healing was evaluated by mechanical testing day 7 after surgery and by flow cytometry day 3 and 10.
RESULTS
Cross-sectional area, peak force and stiffness were reduced by parecoxib 31, 33, and 25% respectively (p=0.005, p=0.002, and p=0.005). By flow cytometry, there was a strong effect of time (p<0.001) on virtually all inflammatory cell subpopulations (CD45, CD11b, CD68, CCR7, CD163, CD206, CD3, CD4), but no significant effect of parecoxib at any time point.
CONCLUSION
The results suggest that the negative effects of Cox inhibitors on tendon healing might be exerted mainly via mechanisms not directly related to inflammatory cells.
背景
在肌腱愈合早期，再生组织中的细胞在很大程度上是炎性白细胞（CD45）。在大鼠跟腱愈合模型中，炎症在5至10天内消退。在同一模型中，环氧化酶抑制剂（非甾体抗炎药）在最初5天内给药会损害愈合，但如果稍后给药则有积极作用。我们检验了这样一个假设，即环氧化酶抑制剂会通过影响炎症，进而影响炎性细胞亚群的组成来发挥这些作用。
方法
对44只动物进行跟腱横断术。将动物随机分为帕瑞昔布注射组或生理盐水注射组。在术后第7天通过力学测试评估愈合情况，并在第3天和第10天通过流式细胞术进行评估。
结果
帕瑞昔布使横截面积、峰值力和刚度分别降低了31%、33%和25%（p = 0.005、p = 0.002和p = 0.005）。通过流式细胞术，时间对几乎所有炎性细胞亚群（CD45、CD11b、CD68、CCR7、CD163、CD206、CD3、CD4）都有显著影响（p < 0.001），但在任何时间点帕瑞昔布均无显著影响。
结论
结果表明，环氧化酶抑制剂对肌腱愈合的负面影响可能主要通过与炎性细胞不直接相关的机制发挥作用。
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