Effect of improving water on endoplasmic reticulum stress in fluoride exposed rats / 中华地方病学杂志

ABSTRACT

Objective To analyze the changes of endoplasmic reticulum stress (ERS) in the spleen of water-improving fluorosis rat,to explore the mechanism of fluoride-induced immune system damage,and to provide a scientific basis for prevention and control of endemic fluorosis.Methods Forty-eight male Wistar rats of SPF grade were randomly divided into control group and low,medium and high fluoride dose groups according to body mass (120-140 g),12 rats in each group.The sodium fluoride (NaF) content was 0,50,100 and 150 mg/L,respectively.The animals were allowed free access to water and food.After 12 weeks of fluoride exposure,6 rats in each group were selected to isolate the spleen;the remaining rats in each group were changed to drink distilled water containing no NaF,and the spleen was separated after 12 weeks of feeding.The levels of mRNA of glucoseregulated protein (GRP78),spliced X-box binding protein 1 (XBP1-s),activating transcription factor 4 (ATF4),homologous protein (CHOP) and cysteine containing aspartate specific protease 12 (Caspase-12) in spleen were determined by quantitative real-time PCR (qRT-PCR).Results Before the water-improving,the expressions of GRP78 (1.00 ± 0.09,1.69 ± 0.35,1.39 ± 0.29,1.19 ± 0.19),XBP1-s (1.00 ± 0.12,1.40 ± 0.23,1.24 ± 0.26,1.38 ± 0.11),ATF4 (1.00 ± 0.17,1.86 ± 0.56,2.33 ± 0.55,1.95 ± 0.74),CHOP (1.00 ± 0.53,2.84 ± 0.68,3.06 ± 1.29,2.50 ± 0.35) and Caspase-12(1.00 ± 0.12,1.90 ± 0.29,1.56 ± 0.35,1.76 ± 0.23) mRNA in the control group and low,medium and high fluoride dose groups were statistically significant (F =8.45,5.38,6.38,8.21,11.31,P ＜ 0.05).Except for the GRP78 in high fluoride dose group,the above indicators in fluoride groups were higher than the control group (P ＜ 0.05).After the water-improving,the expressions of GRP78 (1.00 ± 0.36,0.75 ± 0.13,0.98 ± 0.41,0.47 ± 0.19),XBP1-s (1.00 ± 0.25,0.70 ± 0.06,0.74 ± 0.17,0.65 ± 0.21),ATF4 (1.00 ± 0.51,0.66 ± 0.09,0.91 ± 0.34,0.81 ± 0.29),CHOP (1.00 ± 0.36,0.92 ± 0.12,0.84 ± 0.16,0.67 ± 0.20) and Caspase-12 (1.00 ± 0.45,0.65 ± 0.11,0.65 ± 0.25,0.51 ± 0.27) mRNA in the control group and low,medium and high fluoride dose groups were not statistically significant (P ＞ 0.05).Before and after the water-improving,the expressions of XBP1-s,ATF4,CHOP and Caspase-12 mRNA were statistically significant in fluoride groups (P ＜ 0.05),and the GRP78 only had a statistically significant difference in the low fluoride dose group (P ＜ 0.05).Conclusions Fluoride exposure causes ERS response in rat spleen,up-regulation of ERS-related gene expression,which is decreased after water-improving,and the ERS response is weakened.The water-improving may contribute to the recovery of fluoride-induced immune function damage.