| Atherosclerosis(AS)is a multifactorial and persistent condition and is generally viewed as a chronic inflammation process induced by lipid accumulation.It has been demonstrated that reactive oxygen species(ROS)plays an important role in the chronic inflammatory responses during the development of AS.Selenium nanoparticles(SeNPs)exhibit low cytotoxicity compared to selenium(Se)compounds and posses excellent antioxidant effects,suggesting that SeNPs may have protective effects against AS.In this study,we aimed to elucidate the effects of different doses and different surface modified SeNPs on dyslipidemia and AS lesion in ApoE-deficient mice and the possible mechanisms.Using selenite as a precursor and glutathione as a reductant,biocompatibility BSA-SeNPs were synthesized by the wet chemical reduction method in the presence of bovine serum albumin(BSA).The results of structure characterization revealed that synthesized BSA-SeNPs were amorphous red elementary selenium with the average size 40 nm.Fifty male ApoE-deficient mice aged 6 weeks were divided into 5 groups: AS model group,Statin group(atorvastatin 10mg/kg·bw),BSA-SeNPs group with low(25?g/kg·bw),medium(50?g/kg·bw)and high(100?g/kg·bw)dose of BSA-SeNPs.Mice in all groups were fed with high-fat and high-cholesterol diet.After 12 weeks,serum samples were collected to determine the serum total cholesterol(TC),triacylglycerol(TG),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),glutathione peroxidase(GPx),superoxide dismutase(SOD),malondialdehyde(MDA),nitric oxide(NO)and tumor necrosis factor-alpha(TNF-?)levels.The pathological changes of aortic arch and liver were observed with HE staining and oil red O staining.The levels of TC,TG and the activity of GPx and SOD in liver were detected.In addition,key genes involved in lipid metabolism,selenoenzyme/selenoprotein,pro-inflammatory cytokines in liver and total selenium(Se)contents in different tissues were also measured.The data showed that BSA-SeNPs significantly reduced the levels of TC,TG and LDL-C in serum,the lesions of aortic arch and liver.BSA-SeNPs also significantly reduced MDA levels,and increased GPx and SOD activities and NO levels in serum.Furthermore,BSA-SeNPs upregulated the mRNA levels of selenoenzymes/selenoproteins in liver,and increased Se contents in liver,kidney and cardiac tissues.The effects of medium-dose of BSA-SeNPs were best.The mechanism underlying the anti-atherosclerotic effects of BSA-SeNPs may involve in the antioxidative stress by upregulating the selenoenzyme/selenoprotein mRNA expression levels and enhancing the antioxidant enzyme activites.In addition,BSA-SeNPs also reduced hepatic steatosis levels(TC and TG levels,and lipid peroxidation)and increased the activities of hepatic antioxidant enzymes,and down-regulated the expression of proinflammatory cytokines TNF-? and IL-6.BSA-SeNPs also regulated the expression of key genes related to lipid metabolism,thus reducing lipid accumulation in liver.Using selenite as a precursor and vitamin C as a reductant,biocompatibility CS-SeNPs were synthesized by the wet chemical reduction method in the presence of chitosan.The results of structure characterization revealed that prepared CS-SeNPs were amorphous red elementary selenium with the average size 65.1 nm.Forty male ApoE-deficient mice aged 6 weeks were divided into 4 groups: AS model group,Statin group(atorvastatin 10mg/kg·bw),BSA-SeNPs group(50?g/kg·bw),CS-SeNPs group(50?g/kg·bw).Mice in all groups were fed with high-fat and high-cholesterol diet.After 12 weeks,the same index as described above were detemined.The results showed that BSA-SeNPs were slightly better than CS-SeNPs in reducing blood lipids and inhibiting AS lesions,while CS-SeNPs were much better than BSA-SeNPs in reducing hepatic lesions and decreasing hepatic lipid accumulation. |
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