MON和硒对软骨Ⅱ型胶原的影响及与大骨节病的关系  

The effects of moniliformin toxin and selenium on collagenⅡ and relationship to the pathogenesis of KBD

作　　者：张安[1] 曹峻岭[1] 杨波[1] 陈静宏[1] 张增铁[1] 付强[1] 刘富强[1] 陆敏灵[1] 

机构地区：[1]西安交通大学医学院地方病研究所教育部环境与疾病相关基因重点实验室卫生部微量元素与地方病重点实验室

出　　处：《国外医学（医学地理分册）》2008年第2期49-53,65,共6页Foreign Medical Sciences：Section of Medgeography

基　　金：陕西省科学基金资助项目(2004KW-20);国家自然科学基金资助项目(30471499)

摘　　要：目的大骨节病是一种地方性、慢性、退行性骨关节病,主要损害关节软骨,病变呈对称性。目前,大骨节病病因并不清楚,在我国研究较多的是真菌中毒说和缺硒说。流行病学资料和以往的实验研究表明,串珠镰刀菌素是在大骨节病病区检测到的镰刀菌毒素之一,该毒素在病区、非病区间存在显著差异。因此,串珠镰刀菌素作为大骨节病的可疑致病因子可能与大骨节病的发生、发展具有一定的相关性。Ⅱ型胶原作为软骨细胞外基质主要成分,可以作为软骨损伤的检测指标,该研究的目的就是检测串珠镰刀菌素对软骨细胞和体外再建软骨组织的Ⅱ型胶原的影响,以及硒的保护性作用,为大骨节病是否为真菌毒素和环境缺硒复合因素作用的病因假说提供一些实验证据。方法采用PT-PCR方法检测串珠镰刀菌素毒素对Ⅱ型胶原mRNA的影响;用免疫组织化学的方法检测Ⅱ型胶原、MMP1、MMP13的表达。结果串珠镰刀菌素能够使Ⅱ型胶原mRNA的表达和原位表达均减少,同时MMP1、MMP13的表达增加;补硒能缓解上述变化。结论串珠镰刀菌素毒素能够抑制Ⅱ型胶原mRNA的合成,同时MMP1、MMP13的表达均增加,促进其分解代谢,使Ⅱ型胶原原位表达减少;最终导致软骨细胞损伤甚至变性坏死;补硒能减轻病情严重程度,但并不能完全阻止这些变化。这些都为进一步研究提供了实验证据。Objective Kashin- beck disease （KBD） is an endemic, chronic, degenerative osteoarthropathy manifest in China. At present the etiology and pathogenesis of KBD is unclear. One of the hypotheses is that KBD is caused by fungal myeotoxins on food and a low selenium （Se） environment. The data of epidemiology and empirical study show, moniliformin （MON） is one of fungal myeotoxins has been deteeted in KBD areas, and there is significant deviation from normal areas. So, there is some relationship between MON and the cause of KBD. As a kind of main eomponent, collagen I[ can be detected in order to know the effeet on cartilage tissue when MON was added. The purpose of the study was to investigate the effects of MON on cartilage tissue and investigate the potential beneficial effeets of added Se whieh is thought to abrogate KBD joint pathology. Methods Human ehondroeyte eulture in vitro was treated with MON toxin at different concentrations for varied time periods （5 days）, detected the mRNA of expression by RT- PCR assay. Human articular chondrocytes were cultured on bone matrix gelatin （BMG） as tissue engineered cartilage. The expression of collagen Ⅱ, MMP1 and MMP13 was detected by immunohistochemistry. Results MON could reduce the expression of collagen Ⅱ mRNA in the chondrocytes. MON also could decrease the expression of collagen Ⅱ, and increase the expression of MMP1 and MMP13 in cartilage matrix. The addition of Se partially alleviated this trend. Conclusions MON could restrain collagen Ⅱ synthesis, and could increase collagen Ⅱ catabolism in the cartilage tissue. MMP1 and MMP13 accelerate catabolism of collagen Ⅱ in cartilage matrix. The addition of Se partially alleviated this trend but did not completely abrogate these conditions. All above of these can offer some evidence for KBD research.

关 键 词：软骨组织 串珠镰刀菌素 Ⅱ型胶原 硒 大骨节病 

分 类 号：Q581[生物学—生物化学] R684.1[医药卫生—骨科学]