振动疗法作为一种有效方法改善糖尿病大鼠的骨愈合。
Vibration therapy as an effective approach to improve bone healing in diabetic rats.
机构信息
Department of Orthopaedics and Anaesthesiology, Ribeirão Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil.
Laboratory of Molecular Biology, Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, Ribeirão Preto, SP, Brazil.
出版信息
Front Endocrinol (Lausanne). 2022 Aug 19;13:909317. doi: 10.3389/fendo.2022.909317. eCollection 2022.
OBJECTIVE
To investigate the effects of vibration therapy on fracture healing in diabetic and non-diabetic rats.
METHODS
148 rats underwent fracture surgery and were assigned to four groups: (1) SHAM: weight-matched non-diabetic rats, (2) SHAM+VT: non-diabetic rats treated with vibration therapy (VT), (3) DM: diabetic rats, and (4) DM+VT: diabetic rats treated with VT. Thirty days after diabetes induction with streptozotocin, animals underwent bone fracture, followed by surgical stabilization. Three days after bone fracture, rats began VT. Bone healing was assessed on days 14 and 28 post-fracture by serum bone marker analysis, and femurs collected for dual-energy X-ray absorptiometry, micro-computed tomography, histology, and gene expression.
RESULTS
Our results are based on 88 animals. Diabetes led to a dramatic impairment of bone healing as demonstrated by a 17% reduction in bone mineral density and decreases in formation-related microstructural parameters compared to non-diabetic control rats (81% reduction in bone callus volume, 69% reduction in woven bone fraction, 39% reduction in trabecular thickness, and 45% in trabecular number). These changes were accompanied by a significant decrease in the expression of osteoblast-related genes (), as well as a 92% reduction in serum insulin-like growth factor I (IGF-1) levels. On the other hand, resorption-related parameters were increased in diabetic rats, including a 20% increase in the callus porosity, a 33% increase in trabecular separation, and a 318% increase in serum C terminal telopeptide of type 1 collagen levels. VT augmented osteogenic and chondrogenic cell proliferation at the fracture callus in diabetic rats; increased circulating IGF-1 by 668%, callus volume by 52%, callus bone mineral content by 90%, and callus area by 72%; and was associated with a 19% reduction in circulating receptor activator of nuclear factor kappa beta ligand (RANK-L).
CONCLUSIONS
Diabetes had detrimental effects on bone healing. Vibration therapy was effective at counteracting the significant disruption in bone repair induced by diabetes, but did not improve fracture healing in non-diabetic control rats. The mechanical stimulus not only improved bone callus quality and quantity, but also partially restored the serum levels of IGF-1 and RANK-L, inducing bone formation and mineralization, thus creating conditions for adequate fracture repair in diabetic rats.
目的
研究振动治疗对糖尿病和非糖尿病大鼠骨折愈合的影响。
方法
148 只大鼠接受骨折手术，并分为四组：（1）SHAM：体重匹配的非糖尿病大鼠；（2）SHAM+VT：非糖尿病大鼠接受振动治疗（VT）；（3）DM：糖尿病大鼠；（4）DM+VT：糖尿病大鼠接受 VT 治疗。糖尿病通过链脲佐菌素诱导 30 天后，动物行骨骨折，然后进行手术稳定。骨折后 3 天，大鼠开始接受 VT。通过血清骨标志物分析在骨折后 14 天和 28 天评估骨愈合，收集股骨进行双能 X 射线吸收法、微计算机断层扫描、组织学和基因表达分析。
结果
我们的结果基于 88 只动物。与非糖尿病对照大鼠相比，糖尿病导致骨愈合明显受损，骨密度降低 17%，与形成相关的微观结构参数降低（骨痂体积减少 81%，编织骨比例减少 69%，小梁厚度减少 39%，小梁数量减少 45%）。这些变化伴随着成骨相关基因表达的显著下降（），以及血清胰岛素样生长因子 I（IGF-1）水平下降 92%。另一方面，糖尿病大鼠的吸收相关参数增加，包括骨痂孔隙率增加 20%，小梁分离增加 33%，I 型胶原 C 端末端肽水平增加 318%。VT 增强了糖尿病大鼠骨折部位成骨和软骨细胞的增殖；增加了循环 IGF-1 水平 668%，骨痂体积增加 52%，骨痂骨矿物质含量增加 90%，骨痂面积增加 72%；并与循环核因子κβ配体受体激活剂（RANK-L）减少 19%相关。
结论
糖尿病对骨愈合有不利影响。振动治疗能有效对抗糖尿病引起的骨修复的严重破坏，但不能改善非糖尿病对照大鼠的骨折愈合。机械刺激不仅改善了骨痂的质量和数量，还部分恢复了 IGF-1 和 RANK-L 的血清水平，诱导了骨形成和矿化，从而为糖尿病大鼠的骨折修复创造了条件。
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