Effect Of High Fluorine On Vascular Injury And Arteriosclerosis

Objective:Fluorine is one of the necessary microelements in life activities.Fluorosis not only changes the skeletal system,also impairs the non skeletal system.In this experiment, high-fluorine models of New Zealand white rabbits were developed to research the relationship between high fluorine and atherosclerosis,as well as the interaction between high fluorine and high-lipid diet,and to explore the possible mechanisms.Methods:Methods:According to the 2×2 factorial design,20 New Zealand white rabbits were randomly divided into four groups:control group fed with deionized water and basic forage;high-lipid group fed with deionized water and high-lipid forage(0.5%and 7% egg yolk powder were added into the basic forage);high-fluorine group fed with high-fluorine water(the fluorine concentration is 100mg/L)and basic forage; high-fluorine and high-lipid group fed with high-fluorine water(the fluorine concentration is 100mg/L)and high-lipid forage(0.5%and 7%egg yolk powder were added into the basic forage).After six months,the high-fluorine animal models have been developed.Vein blood was taken from the ear vein at 0,3,6 month during the experiment.Serum fluorine levers were measured.After six months,blood was collected for measurement of serum lipid(TC,TG,LDL-c,HDL-c),hemorheology, anti-oxidation capability(SOD,GSH-Px,MDA),radioimmunology(6-keto-PGF1α, TXB2,ET-1)and nitricoxide synthase.Whole blood which is sterile and anticoagulant was tested for the positive rates of cNOS-mRNA and iNOS-mRNA of leukocyte by in-situ hybridization.After that the experimental animals were anesthetized by pentobarbital sodium(35mg/kg BW)and their thoracic aorta,heart and liver are used to determine the pathological stucture and ultrastructure atherosclerotic plaques(by transmission electron microscope and scanning electron microscope).The homogenate of their heart and liver were tested for nitricoxide synthase,cardiac muscle and the anti-oxidation capability(SOD,GSH-Px,MDA)of the liver.Data were analyzed with normal ANOVA and factorial design ANOVA using the SPSS software(SPSS,version 11.5).Results:1.In high-fluorine fed New Zealand rabbits,serum levels of TC,TG,LDL-c significantly increased(P＜0.05).The low,middle and high shear viscosity of whole blood and plasma viscosity significantly increased(P＜0.01 or P＜0.05).The erythrocyte aggregation index,the value of K in the erythrocyte sedimentation equation,volume of packed red cells(VPRC),and the content of profibrin in the blood plasma significantly increased(P＜0.01 or P＜0.05).2.In high-fluorine fed New Zealand rabbits,the activity of SOD and GSH-Px in serum,cardiac muscle and liver decreased(P＜0.01 or P＜0.05),serum and liver MDA levels increased(P＜0.01);Plasma 6-keto-PGF_1αlevels decreased(P＜0.01),ET-1 levels increased(P＜0.01);total activity of serum NOS decreased(P＜0.01),total activity of liver NOS,cardiac muscle and liver iNOS increased(P＜0.05),the expression of iNOS—mRNA in white blood cell increased while the expression of eNOS—mRNA in white blood cell decreased(P＜0.05).3.In high-fluorine fed New Zealand rabbits,arteriae aorta structure was damaged; structure and arrange of arteriae aorta endothelial cell changed;abundant of celluloses and red blood cells as well as some lipid droplet deposited.4.Analysed by factorial design ANOVA,the index of TC,LDL-c,the low,middle and high shear viscosity of whole blood,erythrocyte aggregation index,the value of K in the erythrocyte sedimentation equation,the red blood cell rigidity index and VPRC, activity of SOD in serum,cardiac muscle and liver,serum MDA level,plasma ET-1 level,serum iNOS activity and liver total NOS activity indicates that there's significant synergistic action between high fluorine and high lipid(P＜0.0 or P＜0.05).Conclusion:1.High fluorine can increase serum TC,TG and LDL-c level in New Zealand rabbits, and further result in lipid metabolic disorder.2.High fluorine can increase New Zealand rabbit's plasma viscosity and erythrocyte aggregation,decrease red blood cell rigidity,thus induces the disorder of blood stream change.3.High fluorine can decrease New Zealand rabbit's serum and tissue antioxidant enzymes activity,increase lipid peroxide level,and further induce widely lipid peroxide in body.4.High fluorine can decrease plasma 6-keto-PGF_1αlevel,and increase plasma ET-1 level in New Zealand rabbits,which induce vasoconstriction and platelet aggregation.5.High fluorine can decrease serum total NOS activity,increase iNOS activity of the heart and liver,and change NOS-mRNA expression and NO level in New Zealand rabbits.6.High fluorine can significantly damage the arteriae aorta endothelium,change endothelial cell structure and arrangement,and induce abundant of celluloses and red blood cells as well as some lipid droplet deposited.In summery,high fluorine can accelerate the formation of atherosclerosis.High fluorine and high lipid have synergistic action in this process.