Aydin Ali, Halici Zekai, Akpinar Erol, Aksakal A Murat, Saritemur Murat, Yayla Muhammed, Kunak C Semih, Cadirci Elif, Atmaca H Tarik, Karcioglu S Sena
Department of Orthopedics and Traumatology, Ataturk University Faculty of Medicine, 25240, Erzurum, Turkey.
J Bone Miner Metab. 2015 Sep;33(5):496-506. doi: 10.1007/s00774-014-0622-6. Epub 2014 Oct 9.
The purpose of this study was to examine the effects bosentan (which is a strong vasoconstrictor) on bone fracture pathophysiology, and investigate the roles of the nonselective endothelin 1 receptor blocker bosentan on the bone fractures formed in rats through radiographic, histopathologic, and immunohistochemical methods. The rats were divided into three groups (six rats in each group): a femoral fracture control group, a femoral fracture plus bosentan at 50 mg/kg group, and a femoral fracture plus bosentan at 100 mg/kg group. The femoral fracture model was established by transversely cutting the femur at the midsection. After manual reduction, the fractured femur was fixed with intramedullary Kirschner wires. The radiographic healing scores of the bosentan 100 and 50 mg/kg groups were significantly better that those of the fracture control group. The fracture callus percent of new bone in the bosentan 100 mg/kg group was significantly greater than that in the control group. Also, semiquantitative analysis showed higher positive vascular endothelial growth factor and osteocalcin staining and lower positive endothelin receptor type A staining in the treatment groups than in the control group. Bosentan treatment also decreased tissue endothelin 1 expression relative to that in the fracture control group. As a result of our study, the protective effect of bosentan was shown in experimental femoral fracture healing in rats by radiographic, histopathologic, and molecular analyses.
本研究的目的是研究波生坦（一种强效血管收缩剂）对骨折病理生理学的影响，并通过影像学、组织病理学和免疫组织化学方法研究非选择性内皮素1受体阻滞剂波生坦在大鼠骨折形成中的作用。将大鼠分为三组（每组六只）：股骨骨折对照组、股骨骨折 + 50 mg/kg波生坦组和股骨骨折 + 100 mg/kg波生坦组。通过在股骨中段横向切割建立股骨骨折模型。手法复位后，用髓内克氏针固定骨折的股骨。波生坦100和50 mg/kg组的影像学愈合评分明显优于骨折对照组。波生坦100 mg/kg组新骨的骨折痂百分比明显高于对照组。此外，半定量分析显示，治疗组中血管内皮生长因子和骨钙素染色的阳性率高于对照组，而A型内皮素受体染色的阳性率低于对照组。与骨折对照组相比，波生坦治疗还降低了组织内皮素1的表达。我们的研究结果表明，通过影像学、组织病理学和分子分析，波生坦在大鼠实验性股骨骨折愈合中显示出保护作用。
