Intervention Of Chondroitin Sulfate On Brain Damage Caused By Chronic Fluorosis In Rats

Objective To explore the mechanism of CNS damage and gender difference and explore the approach of reduce the damage caused by chronic fluorosis.Methods Fed with different concentration of sodium fluoride for 180 day and then successive injected with chondroitin sulfate for 5 days.Statistics of monthly drinking water in each group and body weight after the end of the experiment.The pathologic change was observed by hematoxylin-eosin staining,the distribution and expression of phospho-Erk1/2,MMP2,MMP9,GluR1,GluR2,GFAP,β-tubulin Ⅲ and synaptophsin in cortex and hippocampal CA4 area of rats were detected by Immunohistochemistry,the expression of Erk1/2,phospho-Erk1/2,MMP2,MMP9,Erk1/2,GluR1,GluR2,GFAP,β-tubulinⅢ and synaptophsin at protein level in cortex and hippocampal of rats were detected by Western blotting.Results: There was no significant difference in the amount of drinking water in each group.The weight of the low-dose fluoride group and the high-dose fluoride group was significantly lower than that of the control group,and the high-dose fluoride group was higher than the low-dose fluoride group.The cortex and hippocampal eosinophilic change,neuron loss and arrangement disorder were observed.There are no obvious pathological change in the control group and the treatment group,while the obvious pathological change can be found between the fluoride exposed group and the treatment group.Immunohistochemistry results showed that the increased of phospho-Erk1/2 was found in fluorosis group(P<0.05),the expression of MMP2 was significantly decreased while MMP9 was significantly increased in fluorosis groupcomparing to control(P<0.05),the decreased tendency of GluR1,GFAP,β-tubulinⅢand synaptophsin was found in fluorosis group(P<0.05),the expression of GluR2 is significantly increased in fluorosis group(P<0.05).the increased of Erk1/2,phospho-Erk1/2 at protein levels was found in fluorosis group,the expression of MMP2 was significantly decreased while MMP9 was significantly increased in fluorosis group comparing to control(P<0.05).The decreased tendency of GluR1,GFAP,β-tubulinⅢand synaptophsin at protein levels was found in fluorosis group(P<0.05),the expression of GluR2 at protein levels is significantly increased in fluorosis group(P<0.05).Conclusion: Central nervous system damage caused by chronic fluorosis may be related to changes in extracellular matrix,chondroitin sulfate may reduce the damage to some extent,tripartite synapse are involved in pathogenesis and intervention,and there are differences in the onset and treatment of chronic fluorosis between male and female.