Abstract:

Abstract：Objective To observe the effect of different concentrations of fluoride on the expression of endoplasmic reticulum（ER）chaperone GRP78 and caspase-12 in osteoblasts of rat bone and explore the mechanism of fluorosis of bone in rats. Methods Totally 48 Wistar rats were randomly divided into four groups：in Group A（control group），the rats drunk tap water for 8 weeks；in the B，C，D groups，the rats were treated with NaF in drinking water whose concentration was 50，100，150mg/L，respectively for 8 weeks. Morphology and immunohistochemistry were used to detect the changes of the osteoblasts and the expression of GRP78 and caspase-12 in rat bone. SPSS 13.0 software package and metamorph microscope image analysis system were used to analyze the data. Results Typical symptoms of dental fluorosis were found in the experimental group. The expressions of endoplasmic reticulum chaperone GRP78（F = 7.493，P < 0.05） and caspase-12（F = 12.16，P < 0.05）were of significant differences in B，C，D groups compared with the A group. Conclusions The results suggest that the excessive fluoride initiates the ER stress response in osteoblasts，and may lead to apoptosis.

Key words: fluoride；osteoblast；endoplasmic reticulum stress；78 ku glucose-regulated protein, GRP78；cysteme aspartate specific proteinase-12, caspase-12

摘要：

目的 观察不同质量浓度氟化物对大鼠股骨成骨细胞内质网伴侣分子葡萄糖调节蛋白78（GRP78）及半胱天冬氨酸蛋白酶12（caspase-12）表达的影响，探讨内质网应激在氟骨症形成中的可能作用。方法 2012年6月在中国医科大学附属口腔医院中心实验室将48只Wistar大鼠随机分成4组，对照组（A组）饮用常规自来水，染氟组（B、C、D组）分别饮用含氟化钠质量浓度为50、100、150 mg/L的自来水，建立氟中毒动物模型。观察大鼠股骨成骨细胞形态学改变及内质网伴侣分子GRP78及caspase-12表达情况。采用SPSS13.0软件包和MetaMorph显微图像分析软件进行统计学分析。结果 实验组大鼠切牙出现不同程度氟牙症表现，其骨组织免疫组化结果显示，GRP78、Caspase-12呈阳性表达，随着氟浓度增加，其阳性表达均增加，与对照组比较差异均有统计学意义（P < 0.05）。结论 大鼠股骨成骨细胞在一定质量浓度氟化物作用下，GRP78与Caspase-12均出现过表达，表明在高浓度氟作用下，成骨细胞出现内质网应激，进而导致细胞凋亡。

关键词: 氟, 成骨细胞, 内质网应激, 葡萄糖调节蛋白78, 半胱天冬氨酸蛋白酶12