ABSTRACT
Endoplasmic reticulum stress (ERS) is an important defense mechanism. Under the stimulation of various physical and chemical factors, cells respond to a series of signal transduction pathways to determine whether cells are adapted or not. Fluoride can cause impairment to the nervous system of the body, leading to learning, memory and cognitive impairment, but its mechanism is unknown. Studies have shown that the mechanism of fluorosis damage may be related to ERS-mediated apoptosis. In recent years, nervous system injury caused by fluorosis has been widely concerned by researchers, and ERS may play an important role in its mechanism. Therefore, this article will comprehensively explain the possible role of ERS in nervous system injury caused by fluorosis, and provide a new idea for elucidating the pathogenesis of fluorosis.
ABSTRACT
Objective To study the effects of different fluoride concentrations on proliferation and apoptosis of rats' immune cells,and to explore the effects of fluoride on immune function.Methods Sixty male Wistar rats were randomly divided into four groups,and the concentrations of NaF in drinking water for each group (15 rats in each group) were 0,50,100,and 150 mg/L,respectively.They were freely fed water and commercial standard chow.All rats were sacrificed after 12 weeks.Thymus index was calculated.Lymphocyte proliferation activity in the blood was detected by Cell Counting Kit-8 assay.The apoptosis of monocytes in blood was detected by Annexin V/PI method.The apoptosis of lymphocytes in spleen and thymus was detected by Tunal method.Results After 12 weeks of fluoride exposure,the difference in the thymus immune organ index between the four dose groups was statistically significant (F =6.50,P ＜ 0.05);after 12 weeks,the thymus immune organ index of the low and middle dose groups was significantly lower than that of the control group (0.70 ± 0.19,0.84 ± 0.18 vs 1.16 ± 0.33,P ＜ 0.05).There were significant differences in B and T lymphocyte viability between the four dose groups (F =539.97,4.92,P ＜ 0.05).The viability of B lymphocyte in the blood of the middle dose group was significantly lower than those of control group and the low dose group [(58.09 ± 4.59)％ vs (100.00 ± 9.01)％,(106.70 ± 4.82)％,P ＜ 0.05].The viabilities of T lymphocyte in the blood of the low and middle dose groups were significantly lower than that of the control group [(81.11 ± 2.93)％,(75.68 ± 2.34)％ vs (100.00 ± 34.02)％,P ＜ 0.05].The apoptosis rates of blood mononuclear cells in the fluoride-treated groups were significantly increased than that of control group [(48.00 ± 7.45)％,(47.26± 5.94)％,(48.20 ± 3.40)％ vs (32.50 ± 13.70)％,P ＜ 0.05).Immunohistochemistry results showed that the number of apoptotic lymphocytes in the spleen and thymus increased significantly in high dose group.Conclusion Fluoride can reduce the thymus immune organ index of rats,affect the proliferation of lymphocytes in blood,thymus and spleen,and promote apoptosis of lymphocytes,thus affecting the immune function.
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.