| BackgroundAtherosclerotic disease has become the major disease threatens human health,the foam cells generating from mononuclear macrophage are the classical modification in the early stage and propagating in the pathology of atherosclerosis. The CD36 of scavenger receptors on the foam cells generating from monocytes can recognize and swallow ox-LDL,on the other hand the ox-LDL can induce the highly expression of CD36 and than stimulate the uptake of itself, forming the positive feedback loop which lead to the accumulation of cholesterol in the cell and result in the formation of foam cell. After the generation of foma cells, the highly expression of CD36 can induce the monocytes adhere to atheromatous plaque and participate in the inflammation process of vescular wall leading to the propagation of atherosclerosis. Several studies have already proved that calorie restriction and resveratrol have the effect of anti-atherosclerosis and regulate the expression of Sir2. We hope to run a reserch based on the model of foam cell generating from mononuclear macrophage, discuss the function and related mechanisms of CR and Res in the regulation of CD36 in foam cells.ObjectiveTo discuss the inhibitory effect and regulation passways of CR on the CD36 of scavenger receptors in the foam cell generating from monocytes. To find out the possibility and potential mechanism of resveratrol mimic the function of CR. To investigate the influence on the expression of CD36 on human U937 foam cell and mRNA of long life gene SIRT1 and SIRT3.Methods1. When the amonut of human U937 cells come to 1.0×106 /ml, using the final concentration of 100ng/ml of the phorbol 12-myristate 13-acetate and the final concentration of 80ug/ml of human ox-LDL stimulate cells for 48 hours,after oil red O staining,a large mount of lipid droplet can be viewed in the cytoplasm,which correspond to the morphological feature of foma cell,so that establishe the model of human U937 foam cell.2. The U937 foam cells in the density of 1.0×106 /ml are cultured in the different concentration of resveratrol culture medium for 24 hours. To find out the best drug concentration which has less injuryed cell,us the MTT and FCM. 3. After establishing the model of U937 foma cell,using four kinds of culture mediums which are high glucose DMEM,low glucose DMEM,high glucose DMEM combine with resveratrol and high glucose combine with resveratrol and nicotimamide continue to culture cell for another 48 hours. And then randomly divide into four groups:①foam cell model②CR group③Res durg group④Res durg control group.4. To extract the mRNA from the above groups respectively,detect the reverse transportation PCR and examine the expression level of CD36 on scavenger receptors and mRNA of long life gene SIRT1 and SIRT3.Results1. The results from the MMT and FCM tests show the 20um resveratrol could be a proper durg concentration.2. In comparison with foam cell model,it shows a significant decrease in the expression of CD36 mRNA in the CR group(P<0.01),also a decrease in the Res durg group(P<0.05),while there is no significant change in the expression of CD36 mRNA in the Res drug control group(P>0.05);When compared with Res durg group,the expression of CD36 mRNA decrease in the CR group(P<0.05).3. In comparison with foam cell model,the expression of SIRT1mRNA increases in CR group(P<0.05),and the expression of SIRT1 mRNA shows a significant increase in the Res drug group(P<0.01),while there is no significant change in the Res drug control group(P>0.05);When compared with CR group,the expression of SIRT1 mRNA increase in the Res drug group(P<0.05).4. In comparison with foam cell model,the expression of SIRT3 mRNA increases in the CR group(P<0.05),however there is no much change in the expression of SIRT3 mRNA in Res drug group(P>0.05),also there is no significant change in the Res drug control group(P>0.05);When compared with CR group, the expression of SIRT3 mRNA decreses in the Res drug group(P<0.05).Conclusion1. The expression of mRNA of long life genes of SIRT1 and SIRT3 in U937 foam cell can be up-regulated and the level of mRNA of CD36 of scavenger receptors can be down-regulated by calorie restriction, which has an inhibitary effect on the propagation of foam cell.2. Resveratrol can up regulate the expression of SIRT1 mRNA in of long life gene,but has no effect on the expression of SIRT3 mRNA,meanwhile through the up-regulation of expression of SIRT1 to reduce the expression of CD36 mRNA of scavenger receptors in U937 foam cell.3. CR and resveratrol have different regulation on the family of Sir2, what's more the resveratrol has less inhibitary effect on CD36 in foma cell compared with CR,there might be some other passways except the SIRT1 inhibit the CD36 by CR.
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