The Effect Of Selenium On High Fluorine-Induced Arteriosclerosis

Objective:In this experiment,high fluorine-induced arterioslerosis models of New Zealand white rabbits were developed,take selenium as the role of intervention factors,to explore the possibility and mechanisms of selenium prevents and treats arteriosclerosis.Methods:According to the 2×2 factorial design,20 New Zealand white rabbits were randomly divided into four groups:control group,high-fluorine group,right amount-selenium group and high-fluorine & right amount-selenium group.Control group fed with deionized water;high-fluorine group fed with high-fluorine deionized water(the fluorine concentration is 100mg/L);right amount-selenium group fed with right amount-selenium deionized water(the selenium concentration is 1mg/L); high-fluorine & right amount-selenium group fed with high-fluorine and right amount-selenium deionized water(the fluorine concentration is 100mg/L,the selenium concentration is 1mg/L).After six months,the high-fluorine and the right amount selenium animal models have been developed.Vein blood was taken from the ear vein at 0,3,6 month during the experiment.Serum fluorine and selenium 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 eNOS-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.Intercept a piece of the aortic,by 10%neutral formalin-fixed,paraffin-embedded tissue section made for the detection of endothelial cell apoptosis.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,the whole blood rheology was changed, serum levels of TC,TG,LDL-c significantly increased(P＜0.05);The activity of SOD and GSH-Px decreased,MDA levels increased(P＜0.01 or P＜0.05);The expression of iNOS was abnormal;Plasma 6-keto-PGF1_1α levels decreased(P＜0.01),TXB₂ and ET-1 levels increased(P＜0.01 or P＜0.05);Apoptotic index(AI)of endothelial cell increased(P＜0.01);Arterial aorta structure was damaged;structure and arrange of arterial aorta endothelial cell changed;abundant of celluloses and red blood cells as well as some lipid droplet deposited.2.Given right amount-selenium,the serum levels of TC,HDL-c,LDL-c significantly decreased of high-fluorine fed New Zealand rabbits(P＜0.001),the low and middle shear viscosity of whole blood and plasma viscosity significantly decreased(P＜0.01 or P＜0.05),the content of profibrin in the blood plasma significantly decreased(P＜0.01); The activity of SOD in serum increased(P＜0.05),the activity of GSH-Px in cardiac muscle and liver increased(P＜0.01 or P＜0.05),serum and cardiac muscle MDA levels decreased(P＜0.001);Cardiac muscle iNOS decreased(P＜0.05);Plasma TXB₂ levels decreased(P＜0.05);Apoptotic index(AI)of endothelial cell decreased(P＜0.001); Compared with high-fluorine group,rabbits from high-fluorine & right amount-selenium group had healthier arterial aorta.Structure was essentially normal. Structure of arterial aorta endothelial cell was undamaged.Lipid droplet was seen neither in tunica intima nor tunica media. 3.Analysed by factorial design ANOVA,the index of TC,LDL-c,the low and middle shear viscosity of whole blood,plasma viscosity,the value of K in the erythrocyte sedimentation equation and the electrophoretic time of RBC,activity of SOD in serum, cardiac muscle and serum MDA level,cardiac muscle and serum iNOS activity,liver total NOS activity,the positive rates of iNOS-mRNA in white blood cell,plasma 6-keto-PGF_1α and TXB₂ level,AI of endothelial cell indicates that there's significant synergistic action between high fluorine and right amount selenium(P＜0.01 or P＜0.05).Conclusion:1.Right amount selenium can significantly inhibit lipid metabolic disorder and the whole blood rheology abnormal resulted by high fluorine.2.Right amount selenium can increase New Zealand rabbit's serum and tissue antioxidant enzymes activity,decrease lipid peroxide level,and further inhibit widely lipid peroxide in body induced by high fluorine.3.Right amount selenium can inhibit abnormal expression of iNOS induced by high fluorine.4.Right amount selenium can inhibit plasma 6-keto-PGF_1α level decrease and plasma TXB₂ and ET-1 level increase in New Zealand rabbits which induced by high fluorine. And further inhibit vasoconstriction and platelet aggregation.5.Right amount selenium can inhibit endothelial cell apoptosis which induced by high fluorine.6.Right amount selenium can inhibit the damage of arteriae aorta endothelium induced by high fluorine,keep the normal structure of endothelial cell.In summery,high fluorine can accelerate the formation of atherosclerosis,right amount selenium can inhibit this effect.