内质网应激诱导的细胞凋亡在氟致大鼠甲状腺损伤中的作用  

Effects of endoplasmic reticulum stress-induced apoptosis in thyroid injury caused by fluoride inrat

作　　者：于林玉 崔玉山[2] 刘洪亮[3] Yu Linyu;Cui Yushan;Liu Hongliang(Binhai New Area Centers for Disease Control and Prevention,Tianjin 300453,China)

机构地区：[1]天津市滨海新区疾病预防控制中心,300453 [2]天津市疾病预防控制中心环境与健康室 [3]天津市疾病预防控制中心预防医学研究所天津市卫生计生综合监督所

出　　处：《中华预防医学杂志》2018年第11期1182-1187,共6页Chinese Journal of Preventive Medicine

基　　金：国家自然科学基金（81573107、81372934、30972555）;天津市卫生科技攻关项目（14KGl20）;天津市疾病预防控制中心科技基金项目（CDCKYl501）

摘　　要：目的探讨内质网应激诱导的细胞凋亡在过量氟导致的大鼠甲状腺损伤中的作用。方法将40只Wistar大鼠采用随机数字表法分成4组，分别为对照组和低、中、高浓度氟化钠（NaF）染毒组。对照组大鼠饮用自来水，氟离子浓度为0．344mg／L，低、中、高浓度NaF染毒组饮用含NaF浓度分别为5、10、20mg／L的自来水，染毒8个月后每组处死雌雄大鼠各5只。选择电极法检测尿氟浓度情况，光镜下观察甲状腺组织形态，脱氧核糖核苷酸末端转移酶介导的缺口末端标记法（TUNEL）检测甲状腺组织凋亡细胞，RT．PCR和免疫组化法检测甲状腺组织中葡萄糖调节蛋白78（GRP78）和C／EBP同源蛋白（CHOP）的mRNA和蛋白的表达，比较各组间指标差异。结果与对照组f（2．23±0．54）mg／Lmg/L较，低、中、高浓度NaF染毒组尿氟浓度分别为（4．74±1．88）、（7．70±2．82）、（10．50±2．92）mg／L（P〈0．05）。NaF染毒组大鼠甲状腺组织形态发生了明显的变化，可见较多增生小滤泡，甚至无腔细胞团。TUNEL检测发现染毒组大鼠甲状腺凋亡细胞数明显增加，低、中、高浓度NaF染毒组GRP78mRNA表达水平（分别为1．30±0．42、1．39±0．29、1．50±0．27）高于对照组（0．93±0．24），P〈0．05；中、高浓度NaF染毒组CHOPmRNA表达水平（分别为1．17±0．29、1．30±0．26）亦高于对照组（0．91±0．20），P〈0．05。中、高浓度NaF染毒组大鼠甲状腺组织中GPR78蛋白（分别为29．68±4．04、29．90±3．74）和CHOP蛋白的表达水平（分别为4．05±1．62、4．44±1．81）均高于对照组（23．80±6．36、2．27±0．89），P〈0．05。结论过量氟可造成甲状腺损伤，可能与内质网应激诱导的细胞凋亡有关。Objective To explore the effects of endoplasmic reticulum stress-induced apoptosis in thyroid injury of rats caused by excessive fluoride intake. Methods All 40 Wistar rats were randomly divided into four groups, control group, low fluoride group, medium fluoride group and high fluoride group. The rats in control group were fed with tap water （fluoride concentration--0.344 mg/L） and the experimental rats were fed with the water contaminated fluoride with the dose of 5, 10 and 20 mg/L. 10 rats （female： male= 1 ： 1） in each group were sacrificed after 8 months of exposure through drinking water. The contents of urine fluoride were detected by fluorine ion selective electrode method. Morphology of thyroid was observed through light microscope and apoptosis in thyroid were detected by the terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling （TUNEL） assay. The mRNA and protein expressions of glucose-regulated protein 78 （GRP78） and C/EBP homologous protein （CHOP） were analyzed by RT-PCR and immunohistochemistry respectively, and results were compared among groups. Results The contents of urine fluoride in all fluoride treated groups were separately （4.74± 1.88）, （7.70±2.82） and （10.50±2.92） mg/L, which were gradually higher than that of control group （2.23-±0.54） mg/L （P〈0.05）. Morphological changeswere found in thyroid tissues of fluoride treated groups, thyroid follicular hyperplasia or even no cavity cell clusters were observed. Apoptosis in thyroid were notably increased in fluoride treated groups. The mRNA expression levels of GRP78 in all fluoride treated groups were separately 1.30±0.42, 1.39±0.29 and 1.50± 0.27, which were significantly higher than that of control group （0.93± 0.24） （P〈0.05）. And the mRNA expression levels of CHOP in medium and high fluoride groups were separately 1.17±0.29 and 1.30±0.26, which were significantly higher than that of control group （0.91 ± 0.20） （P〈0.05）. The protein expression levels

关 键 词：细胞凋亡 氟化物 内质网应激 甲状腺损伤 

分 类 号：R114[医药卫生—卫生毒理学]