MMPs/TIMPs基因多态性与激素性和酒精性股骨头坏死的关联性及淫羊藿提取物个体化防治研究

Glucocorticoid and acoholic induced femoral head necrosis is a common disease of bone and joint surgery, now become the main risk factors of non-traumatic femoral head necrosis, and increasing year by year. For the pathogenesis of steroid and alcohol -induced osteonecrosis , there have been many studies at home and abroad, for example, lipid metabolism disorders, estrogen disorders, bone metabolism, etc. But the real pathogenesis is not yet clear. In previous studies, We found MMPs/TIMPs system abnormal expression was inter-related with alcohol and steroid-induced osteonecrosis. Herba Epimedium had been shown to prevention and treatment of steroid and alcohol-induced osteonecrosis, but the mechanism is not clear. This project will use tools of bioinformatics, molecular biology, epidemiology, clinical research investigation, screen MMPs / TIMPs single nucleotide polymorphisms (SNPs) sites of Chinese Han population in central and western regions，collect blood samples of steroid and alcohol -induced osteonecrosis, analysis its association with MMPs / TIMPs gene polymorphism and individualized control effect of Epimedium, discussion interact of MMPs/TIMPs gene polymorphism and environmental factors in this diseases, and provide genetic basis for early diagnosis and prevention steroid and alcohol-induced osteonecrosis.

激素性及酒精性股骨头坏死是骨关节外科的常见疾病，现已成为非创伤性股骨头坏死的主要发病因素，且有逐年增加趋势。现阶段对于激素性与酒精性骨坏死发生的病理机制，国内外有过很多研究，例如脂质代谢紊乱，雌激素水平紊乱，骨代谢异常等，但是其真正发病机制尚未明确。在前期研究中，我们发现MMPs/TIMPs系统表达异常与激素性和酒精性骨坏死的发生发展相互关联。而中药淫羊藿被证实能够防治激素性和酒精性骨坏死，但其作用机理尚不明确。本项目利用生物信息学、分子生物学、流行病学、临床调查研究等手段，筛选出中国中西部地区汉族人群MMPs/TIMPs单核苷酸多态性（SNPs）位点，收集激素性和酒精性骨坏死患者血液标本，分析其与MMPs/TIMPs 基因多态性的关联性及中药淫羊藿的个体化防治效果，探讨MMPs/TIMPs基因多态性与环境因素在骨坏死中的交互作用，为早期诊断与防治提供遗传学依据。

在骨科临床工作中，激素性骨坏死是一种常见病、多发病，严重危害人民群众的健康和生活质量，一旦发生股骨头坏死，很难逆转。在前期研究中，我们发现，激素性和酒精性股骨头坏死与MMPs/TIMPs系统的病理改变有关。在本课题中，我们主要从MMPs/TIMPs基因多态性与激素性和酒精性股骨头坏死的关联性进行了相关研究，相关研究成果共发表学术论文15篇，包括14篇SCI收录文章，总影响因子 52.494。研究成果已经在个别医院应用于激素性骨坏死与酒精性骨坏死的个体化预防和治疗。本研究为建立中国人群骨坏死基因库提供重要数据来源；未来可用作骨坏死诊断的分子标志物。为早期发现易感人群提供依据，有利于将目前股骨头坏死的治疗模式从病后手术转移到病前预防，不仅造福于广大患者，而且具有一定的经济和社会意义。