Zhou Meng, Lu Shibao, Lu Guowei, Huang Jiang, Liu Limin, An Shuai, Li Zheng, Shen Huiliang
Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Mol Med Rep. 2017 May;15(5):3186-3192. doi: 10.3892/mmr.2017.6348. Epub 2017 Mar 22.
Remote ischemic post‑conditioning (RIPC) is an established method to activate the hypoxia‑inducible factor‑1α (HIF‑1α) pathway, which is involved in the impairment of fracture healing. However, the role of RIPC in fracture healing remains to be fully elucidated. In the present study, rats received fractures and were divided into two groups: Control and RIPC, in which hind limb occlusion was performed. Rats were sacrificed at 7, 14, 28 and 42 days subsequent to tibial fracture. Micro‑computed tomography was performed to measure healing of the bone tissue and biomechanical testing was used to test mechanical strength. In addition, the effects of hind limb occlusion on the expression of two primary angiogenic mediators, HIF‑1α and vascular endothelial growth factor (VEGF), as well as the osteoblast markers runt‑related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OCN), were determined at the mRNA and protein levels by reverse transcription‑quantitative polymerase chain reaction, western blot analysis and immunohistochemistry. Systemic administration of hind limb occlusion (3 cycles/day, with each occlusion or release phase lasting 10 min) significantly promoted fracture healing and mechanical strength. The present study demonstrated that in rats treated with hind limb occlusion, the expression of HIF‑1α, VEGF, Runx2, ALP and OCN was significantly increased at the mRNA and protein levels, and that RIPC enhances fracture repair in vivo.
远程缺血后处理（RIPC）是一种已确立的激活缺氧诱导因子-1α（HIF-1α）通路的方法，该通路与骨折愈合受损有关。然而，RIPC在骨折愈合中的作用仍有待充分阐明。在本研究中，对大鼠进行骨折并分为两组：对照组和RIPC组，对RIPC组大鼠进行后肢阻断。在胫骨骨折后的第7、14、28和42天处死大鼠。进行微型计算机断层扫描以测量骨组织的愈合情况，并使用生物力学测试来检测机械强度。此外，通过逆转录-定量聚合酶链反应、蛋白质印迹分析和免疫组织化学在mRNA和蛋白质水平上测定后肢阻断对两种主要血管生成介质HIF-1α和血管内皮生长因子（VEGF）以及成骨细胞标志物 runt相关转录因子2（Runx2）、碱性磷酸酶（ALP）和骨钙素（OCN）表达的影响。全身给予后肢阻断（每天3个周期，每个阻断或释放阶段持续10分钟）可显著促进骨折愈合和机械强度。本研究表明，在接受后肢阻断治疗的大鼠中，HIF-1α、VEGF、Runx2、ALP和OCN的表达在mRNA和蛋白质水平上显著增加，并且RIPC可增强体内骨折修复。
