氟化钠对大鼠长骨组织基质金属蛋白酶-13和基质金属蛋白酶组织抑制因子-1mRNA表达的影响  

Effects of sodium fluoride on matrix metal proteinases-13 mRNA and tissue inhibitor of metal protease-1 mRNA in rat bone tissue

作　　者：孙殿军[1] 高彦辉[1] 周令望[1] 于钧[1] 李颖[1] 王宇[1] 

机构地区：[1]哈尔滨医科大学中国疾病预防控制中心地方病控制中心,150081

出　　处：《中国地方病学杂志》2008年第4期364-367,共4页Chinese Jouranl of Endemiology

基　　金：国家自然科学基金（30371251）

摘　　要：目的观察亚慢性氟中毒大鼠长骨组织中基质金属蛋白酶-13（MMP-13）和基质金属蛋白酶组织抑制因子-1（TIMP-1）mRNA的表达和变化，分析亚慢性氟中毒骨组织基质降解的分子机制。方法将雄性Wistar大鼠按体质量随机分成两组，氟化钠组每日饮用含150mg／L氟离子（FL）的水溶液，对照组饮用自来水，共饲养24周．每4周处死一批动物．每组8只。透射电镜观察骨组织中破骨细胞的超微结构病变特点，RT—PCR法检测骨组织中MMP-13 mRNA和TIMP-1 mRNA的表达情况。结果电镜观察可见破骨细胞溶酶体数量减少并伴有溶酶体酶的合成减少。第4、8、12、16、20、24周时，氟化钠组大鼠骨组织MMP-13相对表达量（1．87±0.67、1．87±0．75、1．90±0．73、1.93±0．86、1．88±0．61、1．84±0.53）明显高于对照组（1.24±0．39、1．19±0．27、1．07±0．22、1．15±0．17、1．17±0．18、1．20±0．62），两组比较差异均有统计学意义（t值分别为2．29、2．41、3、07、2．52、3．15、2．22，P〈0．05）；氟化钠组大鼠骨组织TIMP-1相对表达量（1．89±0．77、1．70±0．85、1．61±0．82、1．81±0．84、1．70±0．74、2.06±0．96）亦明显高于对照组（1．07±0．39、0．87±0．49、0．71±0.48、0．99±0．43、0．95±0．46、0．89±0．57）．两组比较差异均有统计学意义（t值分别为2．69、2．19、2．68、2．46、2．43、2．96，P〈0．05）。结论高剂量氟可以持续诱导MMP-13 mRNA和TIMP-1 mRNA的表达，参与氟中毒骨转换过程。Objective To observe the expressions of matrix metal proteinases-13（MMP-13） mRNA and tissue inhibitor of metal protease-1 （TIMP-1 ） mRNA and analyse the molecular mechanism of bone matrix degradation in the progress of rat subchronic fluorosis. Methods Male Wistar rats were randomly divided into two groups according to body weight, i.e. sodium floride group and control group. Rats in the sodium fluoride group were given drinking water containing 150 mg/L F^-, and the animals in the control group were given tap water. The animals were bred for 24 weeks. Every 4 weeks some rats were killed. The change of obsteoclst was observed by transmission electron microscope. The expression levels of MMP-13 mRNA and TIMP-1 mRNA were analyzed by RT-PCR. Results The number of lysosome and the synthesis of lysosoma enzyme in osteoclast were decreased. The expression of MMP-13 mRNA was significantly increased （t = 2.29,2.41,3.07,2.52, 3.15,2.22, P〈 0.05） in rats treated with sodium fluoride （1.87 ± 0.67,1.87 ± 0.75,1.90 ± 0.73,1.93 ± 0.86,1.88 ± 0.61,1.84 ± 0.53）, compared with control group（1.24 ± 0.39, 1.19 ± 0.27,1.07 ± 0.22, 1.15 ± 0.17,1.17 ± 0.18,1.20 ± 0.62）. The expression of TIMP-1 mRNA was significantly inereased（t = 2.69,2.19,2.68,2.46,2.43,2.96, P 〈 0.05） in rats treated with sodium fluoride （1.89 ± 0.77,1.70 ± 0.85,1.61 ± 0.82,1.81 ±0.84,1.70 ± 0.74, 2.06 ± 0.96）, compared with control group （1.07 ± 0.39,0.87 ± 0.49,0.71 ± 0.48,0.99 ± 0.43,0.95 ± 0.46,0.89 ±0.57）. Conclusion High dose fluoride might persistently induce the expressions of MMP-13 mRNA and TIMP-1 mRNA and may be involved in bone turnover.

关 键 词：氟化物中毒 骨和骨组织 基质金属蛋白酶13 金属蛋白酶1组织抑制剂 

分 类 号：R686[医药卫生—骨科学]