氟对大鼠骨组织RBPJ及相关基因表达影响  

Influence of fluoride on RBPJ and related genes in bone tissue of rats

作　　者：陈修文[1] 万昌武[2] 谢春[3] 杨小雪[3] 吴宇[3] 万雯[2] 

机构地区：[1]贵阳医学院病理学教研室,贵州贵阳550004 [2]贵阳医学院法医病理学教研室 [3]贵阳医学院公共卫生学院环境卫生学教研室

出　　处：《中国公共卫生》2016年第2期195-198,共4页Chinese Journal of Public Health

基　　金：贵州省科技厅社会发展攻关资金(黔科合LG字[2012]056号)

摘　　要：目的观察氟染毒大鼠骨组织中核转录抑制因子(RBPJ)、Jag 1和Hes 5蛋白表达变化,探讨Notch通路与氟骨症关系。方法成年SD大鼠24只,随机分为3组:对照组(饮水含氟<1 mg/L),低、高氟组(饮水含氟50、100 mg/L),每组8只;饲养6个月后,收集尿液和骨组织,测定尿氟和骨氟,观察骨组织学变化并测定骨组织系列形态学指标,免疫组化法检测成骨细胞中RBPJ、Jag 1和Hes 5蛋白表达,免疫印迹法和实时荧光定量法分别检测骨组织RBPJ、Jag 1和Hes 5蛋白与mRNA表达量。结果与对照组比较,低、高氟组大鼠尿氟和骨氟[分别为(11.80±1.08)、(18.08±1.13)mg/L和(5 974.76±2 036.13)、(7 996.51±2 669.93)μg/g)]均升高(均P<0.05);染氟组大鼠骨组织呈骨质硬化病理改变;与对照组比较,低、高氟组大鼠骨组织RBPJ蛋白表达[分别为(4.985±0.913)、(4.279±1.507)]均升高,高氟组Jag 1、Hes 5蛋白表达[分别为(0.112±0.024)、(0.128±0.039)]均降低(均P<0.05);与对照组比较,高氟组大鼠骨组织Jag 1、RBPJ mRNA表达量[分别为(0.005 7±0.005 4)、(0.005 5±0.004 4)]降低(均P<0.05)。结论过量氟抑制Notch通路信号,使该通路下游靶基因表达受到抑制,从而促进成骨作用,参与氟骨症发病过程。Objective To observe changes in proteins of recombination signal-binding protein-J kappa（ RBPJ）,Jagged 1（ Jag 1）,and hairy and enhancer of split 5（ Hes 5） in bone tissue of fluorosis rats and to explore the relationship between Notch signaling pathway and skeletal fluorosis. Methods Twenty-four adult Sprague-Dawley rats were randomly divided into 3 groups（ a control group,low- and high-fluoride groups; 8 rats in each group）. The rats of control group were supplied with tap water containing fluoride less than 1 mg / L and those of low- and high-fluoride group were supplied with water containing 50 and 100 mg / L sodium fluoride（ Na F）. All the rats were sacrificed at 6-month of the treatment. The fluoride contents in urine and bone of the rats were measured with fluoride ion selective electrode method. The bone tissues were stained with hematoxylin-eosin and observed for bone histomorphometric analysis. The protein levels of RBPJ,Jag 1,and Hes 5 in osteoblasts were detected with immunohistochemistry. The expressions of RBPJ,Jag 1,and Hes5 protein and mRNA were detected with Western blot and real-time quantitative PCR. Results Compared with those of the control group,the flouride contents in urine and bone were significantly higher in low-（ 11. 80 ± 1. 08 mg / L and5 974. 76 ± 2 036. 13 μg / g） and high-fluoride（ 18. 08 ± 1. 13 mg / L and 7 996. 51 ± 2 669. 93 μg / g） group（ all P〈0. 05）. Osteosclerosis was observed with optical microscope in the rats of low- and high-fluoride group. The protein expressions of RBPJ in the bones of the low-（ 4. 985 ± 0. 913） and high-fluoride group（ 4. 279 ± 1. 507） were significantly higher than that of the control group（ P〈0. 05）,meanwhile the protein expressions of Jag 1 and Hes 5 in the bones of the rats of high-fluoride group（ 0. 112 ± 0. 024 and 0. 128 ± 0. 039） were significantly lower than those of the control group（ both P〈0. 05）. The mRNA expressions of Jag 1 and RBPJ（ 0. 005 7 ± 0. 005 4 and 0. 005 5 �

关 键 词：氟 骨组织 核转录抑制因子(RBPJ) Jag 1 HES 5 

分 类 号：R395.6[哲学宗教—心理学]