The Effects Of DKK1 On The Procession Of EGb-761 Protecting Nerve Function From Injury Induced By Fluoride

Part Ⅰ DKK1 was involved in cognitive impairment induced by FluorideSubject:To evaluate the risk factors of cognitive impairment of elders in high fluoride drinking water area and investigate whether DKK1 is involved in this disorder.Methods:MoCA-B and AD-8 were used to measure the cognitive functions of 578 elders in high and normal fluoride drinking water area,general information and 15 ml vein blood were collected,the level of SOD,GSH and MDA were measured,mRNA level of DKK1,the concentration of blood fluoride and the polymorphism of APOE were tested.Result:(1)The scores of MoCA-B were lower in elders of high fluoride dinking water area than these in normal fluoride drinking water area.(2)The level of blood fluoride was higher in high fluoride drinking water area,but both of them were normal.(3)The level of SOD and MDA were higher in high fluoride drinking water area,while the level of GSH had no change.(4)The mRNA level of DDK1 was higher in elders of high fluoride area.(5)Age,education and dental fluorosis were the risk factors of cognitive impairment induced by fluorideConclusion:Cognitive impairment could be induced by high fluoride drinking water and DKK1 may be involved in this process.Part Ⅱ EGb-761 attenuate the damages of PC-12cells induced by fluoride sodium via DKK1Subject:To investigate the damage of PC-12cells induced by fluoride and the effects of EGb-761 on the procession.Method:PC-12 cells were treated with different concentrations of fluoride sodium at different time points and CCK8 was used to test their activities.The model of neuron damage induced by fluoride was established.Westernblot was used to measure related proteins of wnt pathway signal,such as GSK-3β、p-GSK-3β and β-catenin.The level of DKK1 was also tested.Furthermore,the apoptosis and proliferation of PC-12 cells exposure to fluoride sodium were investigated.Results:(1)The activity of PC-12 cells decreased significantly until the concentration of Fluoride sodium arriving at 1000μM.EGb-761 and LicL could enhance the activity of PC-12 cells treated with fluoride sodium(2)The expression of DKK1 increased and β-catenin decreased significantly in PC-12 cells treated with high fluoride.(3)Fluoride inhibited the proliferation and promoted the apoptosis of PC-12cells.EGb-761 could attenuate the effects of fluoride sodium.(4)When pretreated with EGb-761 and LicL,the expression of DKK1 and p-GSK-3β decreased significantly and the expression of β-catenin,C-myc and CyclinD increased significantly in fluorosis cell model.Conclusion:DKK1 play an important role in inhibiting proliferation and enhancing apoptosis of PC-12 cells induced by fluoride.EGb-761 could attenuate the impairment of cells induced by fluoride through activating wnt signal pathway via DKK1.