中文摘要：

目的：通过研究不同浓度氟对大鼠切牙成釉细胞基质金属蛋白酶（MMP-20）和基质金属蛋白酶组织抑制剂（TIMP-2）表达的影响,探讨氟斑牙的发病机制,并通过比较给氟组与加褪黑素组MMP-20、TIMP-2表达的差异,探讨褪黑素是否对氟斑牙的发生有拮抗作用。方法：40只Wistar大鼠随机分为6组,分别为对照组（A）、低氟组（B）、高氟组（C）、低氟组加褪黑素组（D）、高氟组加褪黑素组（E）和对照组加生理盐水组（F）,建立氟斑牙动物模型。用HE染色和免疫组化染色观察不同浓度的氟及褪黑素对大鼠切牙成釉细胞的形态及MMP-20、TIMP-2表达的影响,采用MetaMorph显微图像分析系统和SPSS12.0软件包,分别进行图像和数据统计学分析。结果：给氟组大鼠切牙牙面出现白垩色改变,可见釉质表面横纹;成釉细胞形态发生改变,细胞排列紊乱,甚至成灶性堆积,可见空泡性变;MMP-20、TIMP-2在分泌期成釉细胞、成牙本质细胞均有表达,MMP-20在低氟组、高氟组的表达均显著低于对照组（P﹤0.01）,但低氟组和高氟组之间无显著差别;TIMP-2在对照组和高氟组的表达差异有显著性（P﹤0.01）,对照组和低氟组、低氟组和高氟组表达均无显著差别（P﹥0.05）。褪黑素组与未加褪黑素组两者的表达无显著差别。结论：过量氟可抑制MMP-20的表达,使MMP-20/TIMP-2的表达失衡,成釉基质蛋白清除延迟,导致釉质矿化不良,形成氟斑牙,褪黑素对氟斑牙的形成无拮抗作用。

英文摘要：

PURPOSE： To study the effect of concentration of fluoride on the expression of matrix metalloproteinase-20（MMP-20） and tissue inhibitors of metalloproteinase-2（TIMP-2） in the ameloblast of rat incisor,and explore the formation mechanism of dental fluorosis.By comparing the different expression of MMP-20,TIMP-2 between fluoride group and the melatonin group,to decide whether melatonin has antagonitic effect on dental fluorosis.METHODS： Forty Wistar rats were randomly divided into 6 groups.The groups were as follows： control group,low-dose group,hig0h-dose group,normal saline group and melatonin group.The animals were sacrificed 10 weeks after treatment.HE and immunohistochemical staining were used to observe the changes of ameloblasts and the expression of MMP-20 and TIMP-2 in rat incisors.MetaMorph microscope images analysis system was used to analyze the images,and SPSS12.0 software package was used for data analysis.RESULTS： The surface of rat incisors fed with fluoride had chalky color change and cross stritations could be seen on the enamel surface.In the fluoride group,the ameloblasts were disarranged,cells arranged in multi-layer,even showing vacuolar change.The changes in the high-dose group was severer than the low-dose group.MMP-20,TIMP2 were expressed both in the secretory ameloblasts,and in the odontoblasts.The expression of MMP-20 in rat＇s ameloblasts in the experimental group was significantly lower than that in the control group（P﹤0.01）;and no significant difference was found between the low-dose and high-dose groups（P〉0.05）.The difference of expression of TIMP-2 was not significant among all the groups.The difference of expression of MMP-20 and TIMP-2 was not significant between the melatonin and the fluoride groups.CONCLUSIONS： The excessive fluoride can inhibit the secretion of MMP-20 and disturb the balance between MMP-20 and TIMP-2,which lead to the delay of amelogenin removal and enamel demineralization.Melatonin has no antagonistic effect on the dental fluorosi