中文摘要：

目的 探讨不同程度的氟中毒是否影响染氟大鼠软骨组织中COLIXA3蛋白的表达.方法 选用3～4周龄健康雄性Wistar大鼠40只,按体质量随机分为5组,每组8只,分笼饲养,期间分别自由饮用含氟化钠0（对照）、25、50、100、150mg/L的蒸馏水,饲喂6月后建立氟中毒大鼠模型.应用光学显微镜分析实验大鼠骨组织的病理形态学变化过程.并采用免疫组织化学技术检测大鼠股骨干骺端COLIXA3蛋白的表达情况.结果 大鼠骨组织HE染色显示,各染氟组股骨干骺端出现不同程度软骨骨化,骨密度增加,具有硬化性氟骨症病变.对照组软骨组织未见明显异常.大鼠软骨细胞COLIXA3免疫组织化学染色结果为阳性,胞浆内可见有棕黄色颗粒,25、50、100 mg/L组在软骨组织中COLIXA3蛋白表达（23.3±4.5、41.2±5.6、26.4±7.5）增强.其中50、100 mg/L组表达与对照组（6.1±3.5）相比明显增加,组间比较差异有统计学意义（P均〈0.05）.150 mg/L组COLIXA3蛋白（13.3±4.2）较前面3组表达减弱,仍高于对照组,组问比较差异无统计学意义（P〉0.05）.结论 动物模型中,大鼠病理学为单纯性骨硬化表现.低剂量氟促进,高剂量抑制大鼠软骨细胞的增生.随着染氟时间的延长,外环境中氟浓度过高时,对软骨细胞就表现为氟离子的直接毒性作用.氟化物影响染氟大鼠软骨组织中COLIXA3蛋白的表达,低剂量氟可以促进COLIXA3蛋白的表达,随剂量增加氟的促进作用减弱.

英文摘要：

Objective To explore whether different degrees of fluorosis influence the expression of cartilage COLIXA3 protein in fluorosis model rats. Methods Forty male Wistar rats 3 to 4 weeks old were randomly divided into 5 groups according to body mass, and these rats were fed with distilled water containing sodium fluoride（NaF） of 0（control）, 25, 50, 100 and 150 mg/L for 6 months, respectively, in order to establish the animal model of drinking water type fluorosis. Pathomorphologieal changes of the osseous tissues of rats were analyzed under light microscope and transmission electron microscope, and the expression of COLIXA3 protein of femur metaphysis was examined by immunohistochemistry. Results HE staining showed different degrees of femoral metaphyseal ossification of cartilage in each experimental group, bone density increased, with sclerotic lesions of skeletal fluorosis. The control group showed no abnormal cartilage. Electron microscopy showed that the experimental groups with varying degrees of cartilage cell swelling, cell matrix fades, 50 mg/L group .showed hyperplasia, and 100,150 mg/L groups were observed with organelles decreased, part of the disintegration of the cartilage cell lacunae, lmmunohistochemical staining of rat chondrocytes COLIXA3 was positive, cytoplasm with brown granules, cartilage COLIXA3 protein expression（23.3 ± 4.5, 41.2 ± 5.6, 26.4 ~ 7.5） in the 25, 50 and 100 mg/L groups enhanced. Compared to the control group （6.1 ± 3.5）, the expression of 50 and 100 mg/L groups was significantly increased, and the differences were statistically significant（all P 〈 0.05）. The expression（13.3 ± 4.2）of COLIXA3 protein in 150 mg/L group was decreased compared with the previous three, but is still higher than that of control, and the difference was not statistically significant（P 〉 0.05）. Conclusions There has pathological changes of sclerosing skeletal fluorosis in animal model. Low-dose fluoride promotes while high-dose inhibits cartilage cell proliferation. When f