骨组织神经在糖皮质激素诱发缺血性股骨头坏死中作用及机制研究

Glucocorticoid(GC) treatment frequently causes avascular necrosis of the femoral head(ANFH). Since the precise mechanism in the pathogenesis of GC-induced ANFH remains highly controversial, there is no known prophylactic treatment.At the same time, normal bone metabolism requires a coordinated interaction between the sensory/sympathetic nervous system and cells within the bone tissue. So,we speculated that neural lesions of bone may be involved in GC-induced ANFH. And,We investigated the quantitative changes in CGRP-IR nerve fibres, SP-IR nerve fibres, VIPIR nerve fibres, NPY-IR nerve fibres, and NGF-IR that occur in GC-induced ANFH using 24-month-old female Japanese white rabbits.And we found significant changes were seen in the expression of CGRP, SP, VIP and NPY nerve fibres and of NGF immunoreactivity in the subchondral bone of the femoral head and these changes were associated with the process of GC-induced ANFH. We hypothesize four possible mechanisms by which a neural lesion may induce ANFH after GC administration: imbalance in bone metabolism,disturbance in the microcirculation of bone,absence of protective pain-transmission and abnormality in bidirectional regulation through effects on NGF..This research intend to certificate there are four possible mechanisms by molecular biology technique and so on ,using rabbit model of GC-induced ANFH and rabbit model of bilateral sciatic and femoral denervation.Our research will contributed to a better understanding of the molecular processes underlying GC-induced ANFH.And, in addition, foster the option of local therapeutic intervention using neuropeptides. The understanding of the role of neural factors in GC-induced ANFH，is a prerequisite to developing such novel therapeutic options for the treatment of GC-induced ANFH and restoration of tissue function.

糖皮质激素（GC）诱发缺血性股骨头坏死（ANFH）已成为非创伤性ANFH的首要病因之一，其发病机制仍不清楚则是其防治困难的最主要原因。本研究以前期实验发现"GC诱发ANFH发生、发展过程中股骨头局部骨组织神经肽表达有显著性改变"为切入点，提出骨组织神经在GC诱发ANFH发生、发展中起重要作用。.本项目在成功复制的单纯GC诱发ANFH兔模型基础上，拟建立股骨失神经支配兔模型为参照，利用分子生物学、免疫组化等技术观察在GC诱发ANFH过程中实验动物血清、相应节段脊髓、股骨头局部骨组织神经肽合成、表达及分布情况，同时检测股骨头局部生物力学、微循环、保护性痛觉传递及骨组织神经与骨组织双向调控等骨神经作用途径指标，旨在分析GC诱发ANFH发生、骨组织神经改变及其作用途径三者之间相关性及相互作用机制，为明确GC诱发ANFH中骨组织神经所起作用及机制及为临床防治寻找可能的干预措施/靶点提供理论依据。

糖皮质激素（GC）诱发缺血性股骨头坏死（ANFH）是非创伤性ANFH的首要病因之一，其防治的困难在于发病机制不清楚。本研究基于前期的实验研究，创新性的提出骨组织神经在GC诱发ANFH发生、发展中起重要作用，并提出相关可能作用途径。本研究以成功复制的单纯GC诱发ANFH动物模型基础上，利用分子生物学、免疫组化等技术，分析了GC诱发ANFH发生发展过程中股骨头局部生物力学、局部微循环、局部保护性疼痛等指标，验证了此前提出的可能作用途径。