Study on the Inhibitory Effect of Ligustrazine on the Formation of Macrophage-derived Foam Cells

OBJECTIVE:To investigate the inhibitory effect of ligustrazine on the formation of macrophage-derived foam cells and its possible mechanism.METHODS:Human acute mononuclear cells(THP-1)were incubated with 160 nmol/L phorbol ester(PMA) for 24 h to differentiate into macrophages;and the macrophages were incubated with oxidized low-density lipoprotein(ox-LDL)culture solution containing 80 mg/L for 24 h to differentiate into macrophage-derived foam cells.And then the cells were randomly divided into blank control group(ox-LDL),model(AngⅡ)group,positive control(valsartan)group,and ligustrazine low,medium and high concentration groups(the mass concentration were 0.025,0.05 and 0.1 g/L).After all cells were respectively incubated with 80 mg/L ox-LDL culture solution for 48 h,oil red O staining was adopted to observe the transformation rate of foam cells,enzyme chemical method was used to determine the content of cholesterol,and real-time quantitative polymerase chain(RT-PCR)and Western blot were conducted to detect expression levels of Acyl-coenzyme A cholesterol acyltransferase-1(ACAT-1)m RNA and its protein.RESULTS:Compared with blank control group,the transformation rate of foam cells and content of cholesterol in model group were increased,and the expression levels of ACAT-1 m RNA and its protein were obviously strengthened,with significant differences(P0.01 or P0.05).Compared with model group,the transformation rate of foam cells and content of cholesterol in positive control group(valsartan)and ligustrazine low,medium and high concentration groups were decreased,and the expression levels of ACAT-1 m RNA and its protein were obviously weakened,with significant differences(P0.01 or P0.05).CONCLUSIONS:Ligustrazine can inhibit the macrophages differentiating into foam cells,by a mechanism that may be related to inhibiting expression of ACAT-1,and reducing content of cholesterol to reduce formation of foam cells.