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-I mRNA were analyzed by RT-PCR. Results The number of lysesome and the synthesis of lysosoma enzyme in osteeclast 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, I. 15 ~ 0.17, 1.17±0.18, 1.20±0.62). The expression of TIMP-1 mRNA was significantly increased (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.%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(F-)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、1184±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條相对表达量(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.
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