Effects of endoplasmic reticulum stress-induced apoptosis in thyroid injury caused by fluoride in rat
10.3760/cma.j.issn.0253-9624.2018.11.017
- VernacularTitle: 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
- Author:
Linyu YU
1
;
Yushan CUI
;
Hongliang LIU
Author Information
1. Binhai New Area Centers for Disease Control and Prevention, Tianjin 300453, China
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Fluoride;
Endoplasmic reticulum stress;
Thyroid injury
- From:
Chinese Journal of Preventive Medicine
2018;52(11):1182-1187
- CountryChina
- Language:Chinese
-
Abstract:
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 changes were 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 of GRP78 and CHOP in medium and high fluoride groups were respectively 29.68±4.04, 29.90±3.74 and 4.05±1.62, 4.44±1.81, which were significantly higher than those in the control group (separately 23.80±6.36, 2.27±0.89) (P<0.05).
Conclusion:Excessive-fluoride intake can induce thyroid injury, and endoplasmic reticulum stress-induced apoptosis might be involved in the injury.
