大骨节病病因与发病机制的研究进展及其展望_临床医学论文.docVIP

大骨节病病因与发病机制的研究进展及其展望_临床医学论文 大骨节病病因与发病机制的研究进展及其展望_临床医学论文 【摘要】 　　大骨节病是一种地方性、畸形性骨关节病，至今原因未明，目前以我国西部地区最重，尚无有效治疗措施。本文依据国内外有关研究，总结分析了大骨节病三种病因假说的研究进展及其尚待解决的问题，结合作者及其研究团队近年来的研究进展，提出大骨节病除经典的软骨细胞坏死外还表现有软骨细胞过度凋亡和“去分化”，大骨节病软骨细胞差异表达基因、血清蛋白表达谱及短串联重复序列多态性不同于病区内外正常人与骨关节病。确定大骨节病软骨细胞坏死发生的基因与蛋白标志物，以及何种环境因素如何与大骨节病易感基因相互作用而选择性的损伤深层软骨细胞及其干预措施，是未来大骨节病病因发病机制研究的重要目标。 【关键词】 大骨节病 病因 发病机制 基因 蛋白组学 　　ABSTRACT: Kashin-Beck disease (KBD) is an endemic and deforming osteochondropathy and its etiology remains unclear up to now. The prevalence of the disease is the severest in the western China and the effective methods for prevention and cure still need further study. This article summarized the progression and problems to be investigated for three main hypotheses of KBD by reviewing literature published at home and abroad. Integrating with his own research work and his team members, the author suggested that excessive apoptosis and dedifferentiation of chondrocytes besides classic chondrocytic necrosis in KBD growth plate and articular cartilage, differences of gene expression profiles in cartilage and peripheral blood mononuclear cells, proteomic markers and short tandem repeat polymorphism in KBD patients were significantly different from those of the healthy subjects from both KBD-areas and non KBD-areas, and those of osteoarthritis patients. The important objectives in the future are to understand ① the gene and proteomic markers for chondrocytic necrosis in KBD, ② environmental factors that cause the damage to KBD chondrocytes, ③ the way it selectively impairs chondrocytes in the deep zone of growth and joint cartilage by interacting with susceptible gene related to KBD, and ④ effective intervention methods. 　　KEY WORDS: Kashin-Beck disease(KBD); etiology; pathogenesis; gene; proteomic marker 　　大骨节病的发生至少可追溯到16世纪，其中病因与发病机制的研究始于N.I.Kashin(1859-1868年)和E.V.Beck(1906-1908年)。从最早苏联、日本学者提出居民膳食和饮水中元素比例失调、水中有机物中毒和食用了镰刀菌污染的谷物致病因素到目前我国深入到分子生物学水平的研究大骨节病病因及发病机制，国内外学者对大骨节病病因及发病机制进行了长期艰苦研究，做出了卓越的贡献。特别是20世纪50