Kaygusuz M Akif, Turan C Cengiz, Aydin N Engin, Temel Ismail, Firat Serpil, Bulut Taner, Kuku Irfan
Inonu University Medical Faculty, Department of Orthopedics, Malatya, Turkey.
Life Sci. 2006 Dec 3;80(1):67-73. doi: 10.1016/j.lfs.2006.08.023. Epub 2006 Aug 25.
Local and systemic release of transforming growth factor beta 1 (TGF-beta1) is known to increase during the process of fracture healing and this cytokine stimulates bone healing. The majority of the non steroidal anti inflammatory drugs (NSAIDs) inhibit fracture healing. Granulocyte colony stimulating factor (G-CSF) is a hematopoietic growth factor that stimulates bone marrow. In this study, the effects of the NSAID naproxen sodium, G-CSF, and both of them in combination on the TGF-beta1 serum level in rats with tibia fractures were measured and fracture healing was evaluated by histopathologic and radiologic examination. The TGF-beta1 serum levels obtained on day one (24 h after fracture but before administration of naproxen or G-CSF) were found to be similar in all of the five groups (p > 0.05). At the end of the first week, TGF-beta1 levels were significantly lower in naproxen-treated rats than those of the other groups excluding control (p = 0.002). Similar changes in TGF-beta1 levels were found at the end of the second and fourth weeks. TGF-beta1 levels were significantly higher in G-CSF-treated rats at the end of the first, second and fourth weeks (p < 0.05). Fracture healing scores measured with histopathological and radiological methods were higher in G-CSF-treated rats than in naproxen-treated ones. When both naproxen and G-CSF were given, the scores resumed to normal. The results point to the negative effect of naproxen sodium on fracture healing is due to its decreasing effect on the level of TGF-beta1, which may be a new possible mechanism. Moreover, this negative effect can be inhibited by the use of G-CSF.
已知在骨折愈合过程中，转化生长因子β1（TGF-β1）的局部和全身释放会增加，并且这种细胞因子会刺激骨愈合。大多数非甾体类抗炎药（NSAIDs）会抑制骨折愈合。粒细胞集落刺激因子（G-CSF）是一种刺激骨髓的造血生长因子。在本研究中，测量了NSAID萘普生钠、G-CSF以及它们两者联合使用对胫骨骨折大鼠血清TGF-β1水平的影响，并通过组织病理学和放射学检查评估骨折愈合情况。发现所有五组在第1天（骨折后24小时，但在给予萘普生或G-CSF之前）获得的血清TGF-β1水平相似（p>0.05）。在第一周结束时，萘普生治疗组大鼠的TGF-β1水平显著低于除对照组外的其他组（p = 0.002）。在第二周和第四周结束时也发现了TGF-β1水平的类似变化。在第一周、第二周和第四周结束时，G-CSF治疗组大鼠的TGF-β1水平显著更高（p<0.05）。用组织病理学和放射学方法测量的骨折愈合评分在G-CSF治疗组大鼠中高于萘普生治疗组。当同时给予萘普生和G-CSF时，评分恢复正常。结果表明，萘普生钠对骨折愈合的负面影响是由于其对TGF-β1水平的降低作用，这可能是一种新的可能机制。此外，这种负面影响可以通过使用G-CSF来抑制。
