基于骨小梁空间结构异常改变双氢青蒿素治疗股骨头坏死的力学机理实验研究

Femoral head necrosis is one of the common diseases in the orthopedics. In recent years, the incidence rate is increasing with more and more femoral neck fracture and the extensive application of glucocorticoid. However, the mechanism is not yet clear.In this study, the mechanism of femoral head osteonecrosis was studied from the point of the mechanical structure of trabecular bone in the femoral head. In this study, the specimens of necrosis femoral head and femoral neck fractures were collected. The morphological structure of the trabecular bone and the thickness of the cartilage in different regions were analyzed by micro-CT, hard tissue and paraffin sections. The trabecular bone structure abnormality was identified in the necrosis femoral head. In the in vitro model, the femoral head specimens were subjected to mechanical loading and three-dimensional finite element analysis to simulate the stress state of the hip joint and the necrosis of the femoral head, and to explore the mechanics metabolism of the trabecular bone during the development of the femoral head necrosis. At last, we established steroid-induced and traumatic-associated femoral head osteonecrosis SD rats model. The rats were administrated with different doses of artemisinin. SPECT/micro-CT was used to identify the bone metabolism during the progression of femoral head necrosis. The changes of trabecular bone structure and bone turnover activity were detected. The important role of trabecular bone mechanics and metabolic abnormalities in the pathogenesis of femoral head necrosis was clarified. This provides a new ideas for clinical treatment of femoral head necrosis.

股骨头坏死作为骨科常见病，其发病机制目前尚不明确，且缺乏有效治疗措施。青蒿素为传统中草药，最新研究发现其对于骨代谢有显著影响，但对于股骨头坏死的治疗作用有待阐明。本研究拟基于骨小梁空间结构异常改变理论，探讨双氢青蒿素对股骨头坏死的治疗作用。首先收集股骨头坏死与股骨颈骨折临床标本，通过生物影像学和病理学技术，比较二者不同区域骨小梁的形态结构差异，明确骨小梁结构异常在股骨头坏死发生发展中的关键作用。在体外模型中，对新鲜股骨头标本进行力学加载及三维有限元力学模拟分析，模拟髋关节过载受力状态和股骨头坏死的发病过程，阐明力学机理通过影响骨小梁形态结构导致股骨头坏死。最后建立激素性和创伤性股骨头坏死的SD大鼠动物模型，并给予不同剂量双氢青蒿素干预，明确其对于股骨头坏死进展过程中骨代谢、骨小梁形态结构及骨转换活性异常改变的保护作用。该研究成果有望为股骨头坏死的早期临床治疗提供实践基础和理论依据。

股骨头坏死作为骨科常见病，其发病机制目前尚不明确，且缺乏有效治疗措施。最新研究发现双氢青蒿素对于骨代谢有显著作用，但对于股骨头坏死的治疗作用有待阐明。本研究基于骨小梁空间结构异常改变理论，探讨双氢青蒿素对股骨头坏死的治疗作用和潜在机制。首先收集正常与坏死股骨头临床标本，并进行Micro-CT扫描和定量计算、石蜡切片HE染色以及OPG、BMP2免疫组织化学染色，结果显示正常与坏死股骨头各个区域存在不同程度的差异，揭示了股骨头内骨小梁空间结构与代谢活性的异常可能是造成坏死和进一步塌陷的主要原因。在体外力学加载实验中，对股骨头标本进行生物力学加载和对比分析，结果显示股骨头各个区域的力学检测结果存在不同程度的差异，提示股骨头自身结构的力学特性在股骨头坏死的启动中发挥着关键作用。通过计算机三维有限元模拟分析研究，得到的实验结果与体外加载实验力学测试结果相一致，表明力学环境改变会降低股骨头内骨小梁生物力学性质，从而为生物力学因素在股骨头坏死发展过程中的作用提供理论支撑。最后分别建立股骨头坏死的细胞模型和动物模型，并给予不同剂量的双氢青蒿素干预，且通过Micro-CT扫描和定量计算、硬组织切片Von kossa染色、石蜡切片HE染色、TRAP染色、免疫组织化学染色及Western blotting等检测，进一步验证双氢青蒿素对股骨头坏死具有治疗作用，且潜在机制可能是通过上调OPG的表达，下调RANK和RANKL的表达，调节OPG/RANKL/RANK信号通路，改变骨代谢异常，进而改善股骨头坏死。通过本研究能够从临床现象发现实际问题，进一步从生物力学角度探究股骨头坏死的发病机制，探讨生物力学因素在股骨头坏死的发生发展和治疗过程中的重要作用，然后结合当前较为热门的中药保髋治疗手段，在体外细胞实验和体内动物实验中分别验证双氢青蒿素对股骨头坏死的治疗作用和潜在机制，该研究成果有望在股骨头坏死的早期治疗方面提供新思路，对临床中股骨头坏死的早期治疗具有指导意义，从而有效减少和避免股骨头坏死给患者带来的痛苦和伤害，造福百姓。