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首页> 外文期刊>Journal of orthopaedic research >Sildenafil accelerates fracture healing in mice.
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Sildenafil accelerates fracture healing in mice.

机译：西地那非可加速小鼠的骨折愈合。

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Sildenafil, a cyclic guanosine monophosphate (cGMP)-dependent phospodiesterase-5 inhibitor, has been shown to be a potent stimulator of angiogenesis through upregulation of pro-angiogenic factors and control of cGMP concentration. Herein, we determined whether sildenafil also influences angiogenic growth factor expression and bone formation during the process of fracture healing. Bone healing was studied in a murine closed femur fracture model using radiological, biomechanical, histomorphometric, and protein biochemical analysis at 2 and 5 weeks after fracture. Thirty mice received 5 mg/kg body weight sildenafil p.o. daily. Controls (n = 30) received equivalent amounts of vehicle. After 2 weeks of fracture healing sildenafil significantly increased osseous fracture bridging, as determined radiologically and histologically. This resulted in an increased biomechanical stiffness compared to controls. A smaller callus area with a slightly reduced amount of cartilaginous tissue indicated an accelerated healing process. After 5 weeks the differences were found blunted, demonstrating successful healing in both groups. Western blot analysis showed a significantly higher expression of the pro-angiogenic and osteogenic cysteine-rich protein (CYR) 61, confirming the increase of bone formation. We show for the first time that sildenafil treatment accelerates fracture healing by enhancing bone formation, most probably by a CYR61-associated pathway.
机译：西地那非是一种环状鸟苷单磷酸（cGMP）依赖性磷酸二酯酶5抑制剂，已被证明是通过上调促血管生成因子和控制cGMP浓度来有效刺激血管生成的。本文中，我们确定西地那非在骨折愈合过程中是否还会影响血管生成生长因子的表达和骨形成。在骨折后2周和5周，采用放射学，生物力学，组织形态计量学和蛋白质生化分析，在小鼠闭合性股骨骨折模型中研究了骨愈合。 30只小鼠接受口服西地那非5 mg / kg体重。日常。控件（n = 30）收到了等量的车辆。经放射学和组织学检查，骨折愈合2周后，西地那非显着增加了骨性骨折的桥接。与对照相比，这导致增加的生物力学刚度。愈伤组织面积较小，软骨组织量略有减少，表明愈合过程加快。 5周后发现差异变弱，表明两组均成功治愈。 Western印迹分析显示促血管生成和成骨的富含半胱氨酸的蛋白质（CYR）61的表达明显较高，证实了骨形成的增加。我们首次显示西地那非治疗通过增强骨骼形成（最可能是通过CYR61相关途径）来加速骨折愈合。

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