基于三元调控理论探讨补肾法对Masquelet技术中诱导膜形成及骨组织重建的干预机制

The Masquelet technique was an important method in treating critical bone defects. while long treatment duration and poor new bone formation, as main accompanied problems were needed to be solved. Tonifying kidney plays exact function on bone formation,and has great potential in treating bone defects, but its application in Masquelet technique has not been reported. In bone formation process, unlike previous two ternary regulation, the CD31hiEmcnhi vessel induced by PDGF-BB from osteoclast precursor cells plays important role, that is vessel formation, osteoblast and osteoclast, so called three ternary regulation. Meanwhile, studies has found osteoclast precursor cells in induced membrane except osteoblast and osteoclast. Therefore, we plan to construct critical bone defect in rat femur and treat it with Masquelet technique, tonifying kidney will be conducted as intervention, the effect of tonifying kidney on osteoblast, osteoclast, osteoclast precursor cells and CD31hiEmcnhi vessel during induced membrane formation and new bone formation will be clarified by histomorphology, radiography and molecular biology. Eventually, we will explore the intervention mechanism of tonifying kidney in Masquelet technique, which is in favor of objectively evaluating the function of traditional Chinese medicine in treating bone defects.

Masquelet技术是治疗大段骨缺损的重要方法，但治疗周期长和新骨形成不佳是其亟待解决的关键问题。补肾法促进骨形成的作用确切，在骨缺损的治疗中也有巨大潜能，但其在Masquelet技术中的应用仍未有报道。骨形成过程中，不同于既往的“二元调控”，由破骨前体细胞分泌PDGF-BB所诱导生成的CD31hiEmcnhi 血管亦有重要作用，即血管形成、成骨细胞和破骨细胞的“三元调控”理论。同时，目前已发现在诱导膜中除成骨细胞、破骨细胞外，还存在破骨前体细胞。因此，本研究拟通过建立大鼠大段骨缺损模型，采用Masquelet技术进行治疗，并给予补肾法干预，从组织形态学、影像学和分子生物学角度,阐明在诱导膜形成期和骨组织重建期，补肾法对成骨细胞、破骨细胞、破骨前体细胞及CD31hiEmcnhi 血管生成的影响，探讨补肾法在Masquelet技术中的干预机制，有利于客观评价中医药在骨缺损治疗中的作用。

Masquelet技术是治疗大段骨缺损的重要方法，但治疗周期长和新骨形成不佳是其亟待解决的关键问题。补肾法促进骨形成的作用确切，在骨缺损的治疗中也有巨大潜能，但其在Masquelet技术中的应用仍未有报道。骨形成过程中，不同于既往的“二元调控”，由破骨前体细胞分泌PDGF-BB所诱导生成的CD31hiEmcnhi 血管亦有重要作用，即血管形成、成骨细胞和破骨细胞的“三元调控”理论。同时，目前已发现在诱导膜中除成骨细胞、破骨细胞外，还存在破骨前体细胞。因此，本研究通过建立大鼠大段骨缺损模型，采用Masquelet技术进行治疗，并给予补肾法干预，从组织形态学、影像学和分子生物学角度,阐明在诱导膜形成期和骨组织重建期，补肾法对成骨细胞、破骨细胞、破骨前体细胞及CD31hiEmcnhi 血管生成的影响，探讨补肾法在Masquelet技术中的干预机制。研究结果显示：骨碎补总黄酮可上调三元调控通路各关键因子PDGF-BB、CD31、Endomucin）及 VEGF、HMGB1 基因、蛋白的表达，骨碎补总黄酮在Masquelet技术中对骨缺损区域的成骨质量和血管形成具有良好的促进作用。