| Atherosclerosis(AS)is a kind of disease that is harmful to human health,in which the formation of a large number of macrophage foam cell by devouring lipid is one of the key steps to AS occurrence and development.Natural product A,a kind of flavonoid,has a variety of pharmacological activities,such as antitumor,antibacterial,anti-cardiovascular newborn,anti-oxidation,anti-aging,anti-diabetes.But whether it can inhibit macrophage foam cells and prevent the occurrence of AS have not been reported.This paper studied the role of natural product A inhibiting macrophage foam,and its mechanism by molecular biology techniques.First of all,we established lipid accumulation model induced by ox-LDL cholesterol on RAW264.7 macrophage cells and used Oil Red O staining and detection kit to observe natural product A inhibition to macrophage foam formation;and then fluorescence quantitative methods to assess the impacts on promoting cholesterol outflow from macrophages;simultaneously measured mRNA expression levels,such as ABCA1,ABCG1,LXRa and PPARy genes which was related to cellular cholesterol efflux,and assessed the activity of PPARy,the most upstream regulatory factor of macrophage cholesterol efflux,by fluorescence experimental determination of luciferase.At the end,we detected cholesterol inflows through detecting the fluorescence intensity and further measured cholesterol inflows mRNA expression levels,such as SR-1,SR-2 and CD36,by real-time PCR.The results show that natural products A significantly suppressed macrophage foam cells induced by ox-LDL cholesterol,and lower total cholesterol(TC)levels.Meanwhile,natural product A can promote cholesterol outflow from RAW264.7 cells,which may be associated with improved the mRNA expression level of ABCAl、ABCG1、LXR and PPARγ,and the transcriptional activity of PPARy.Simultaneously,natural product A may also inhibit the uptake of cholesterol by reducing the transcription level of SR-1 and SR-2. |
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