Effects Of Astaxanthin On Atherosclerosis And Gut Microbiota In ApoE^-/- Mice

The purpose of this study was to investigate the effects of astaxanthin on atherosclerosis and gut microbiota in HFD-induced ApoE^-/-mice.Mice were divided into 7 groups:WT-LFD,WT-HFD,ApoE^-/--LFD,ApoE^-/--HFD,ApoE^-/--ASTL,ApoE^-/--ASTH,ApoE^-/--ATO.Open field and Morris water maze test was used to measure locomotor activity,psychological processes as well as spatial learning and memory ability;Biochemical kits were used to measure serum and hepatic lipids,antioxidant ability;H&E,oil red O,fundus fluorescence angiography（FFA）,CD31 immunohistochemical staining was used to measure histopathological changes of adipose tissue,liver,intestine,aorta and retina;PCR analysis was used to measure the genes expression of hepatic lipids metabolism;16S rRNA highthroughput sequencing and gas chromatography was used to measure the amount gut microbiota,bile acids and SCFAs.After 30 weeks intervention,results showed that astaxanthin significantly inhibited weight gain,reduced serum TC and TG,improved serum HDL-C,relieved lipids accumulations in epididymal fat,liver,aorta,and aortic root.As well as reduced hepatic and serum MDA content,increased the activity of CAT,GSH-PX and SOD.Furthermore,retinal vascular imaging and FFA showed that astaxanthin protected retinal vascular hemangioma,capillary degradation,branch arteriovenous blockage and local variant.Retinal CD31/PECAM-1 immunohistochemical results also showed that the astaxanthin intervention could reduce the expression of CD31 in retinal blood vessels,inhibit the migration of endothelial cells and alleviate the occurrence of fundus atherosclerosis.The results of openfield experiment and Morris water maze experiment showed that astaxanthin could alleviate the decline of behavior,memory and cognitive function caused by hyperlipidemia.Intestine H&E staining showed that astaxanthin could inhibit the shortening intestinal villi and crypt to protect the normal physiological function.The results of gas chromatographic analysis showed that astaxanthin could improve the amount of bile acids and SCFAs.In 16S rRNA high-throughput sequencing analysis,astaxanthin could increase beneficial bacteria related to the amount of secondary bile acids and SCFAs,and the relative abundance of g_Akkermansia.All in all,differing from Lipitor,astaxanthin tent to attenuates atherosclerosis through maintain gut microbiota homeostasis.