基于股骨头内骨陷窝-微管系统介导糖皮质激素损伤理论干预股骨头坏死形成机制探讨

It has been verified the effectiveness of Icariin(ICA) formulation prevention of corticosteroids induced osteonecrosis of femoral head(ONFH) by our pre-organized multi center, random, double blind, placebo controlled clinical study, and recently we also achieved preliminary results from extracorporeal shockwave(ESW) prevent ONFH formation. However, the mechanism remains unknown. Lacunar-canalicular system (LCS) plays a major role in regulating the stability of the bone microenvironment, to maintain normal physiological and immune function, as well as the occurrence, development and prognosis of diseases mediated by other aspects. ICA and ESW may reduce the occurrence of ONFH by prevention of the injury of LCS from steroid. To test this hypothesis, this study will use high-resolution microscopy techniques to assess the lacunar-canalicular microstructure in the rabbit model of osteonecrosis. Confocal microscopy will be analyzed the quantification of osteocyte lacunar-canalicular porosity and lacunar area, canalicular diameter, osteocyte lacunar density, number of canaliculi per lacuna, and lacunar and canalicular volume. The Solute transport functional difference through the bone LCS can be measured using fluorescence recovery after photobleaching (FRAP). And synchrotron radiation phase contrast imaging will be used to detect the microstructure difference in LCS from different groups. This research will investigate the biological effects of ICA and ESW in the prevention of osteonecrosis and elucidate its biological mechanism. Effective prevention in those patients receiving corticosteroids will prevent the onset of ONFH from the source. On the basis of former study, our research group will get expecting achievement.

我中心前期组织多中心、随机双盲、对照评价淫羊藿苷预防激素性股骨头坏死的临床研究，证实了其有效性；同时临床应用体外震波干预股骨头坏死形成取得初步成果，但这些干预方法具体机制仍不明确。骨陷窝-微管网络系统（LCS）在调节骨内微环境的稳定，维持正常生理功能，以及介导疾病的发生、发展和转归等方面都发挥主要的作用。为验证淫羊藿苷和体外震波可能通过干预LCS介导激素损伤而减少骨坏死发生这一假设，使用新西兰大白兔经骨坏死造模，应用淫羊藿苷和体外震波分别干预，取材后用共聚焦激光扫描显微技术定量测定股骨头内骨微管直径、骨陷窝密度、微管数及陷窝微管体积的形态学改变；利用荧光光漂白恢复技术（FRAP）测定LCS功能变化；同时使用同步辐射相位衬度成像检测LCS内微观结构差异。比较分析淫羊藿苷和体外震波干预保护LCS介导激素损伤的作用并探讨其可能机制。为从根源上减少骨坏死这一致残性疾病的发生提供理论基础。

骨陷窝-微管网络系统（Lacunar-canalicular system, LCS）在调节骨内微环境的稳定，维持正常生理功能，以及介导疾病的发生、发展和转归等方面都发挥主要的作用。本研究使用新西兰大白兔建立激素性股骨头坏死造模并进行淫羊藿苷干预，使用Micro-CT扫描及三维重建技术观察股骨头标本显微结构并进行定量分析，使用同步辐射相位衬度成像技术检测LCS内微观结构差异，并通过病理学检测骨陷窝数目及功能变化。本研究发现淫羊藿苷能够降低激素对骨陷窝-微管功能与显微结构的损伤作用，稳定骨小梁结构，降低空骨陷窝率及骨坏死发生率，促进早期股骨头坏死修复，延缓骨坏死发生，具有重要的科研意义及实用价值。