Effects Of Probucol On Atherosclerotic Lesions And SR-BI Expression In Mice

OBJECTIVE: The aim of the study is to investigate the effects of probucol on high fat-high cholesterol diet-induced hyperlipidemia and atherosclerotic lesions, and the expressions of scavenger receptor class B typeⅠand peroxisome proliferators-activated receptor gamma in apo E knockout mice and genetic background C57BL/6J mice.METHODS: Twenty male C57BL/6J mice and twenty apoE^-/- mice were randomly divided into two groups (n=10, each group), respectively. All of the mice were fed a high fat/high cholesterol diet. The intervention groups were supplemented with 0.5% probucol in high fat-high cholesterol diet. After 12 weeks, all animals were killed. Collected blood was prepared to determine the serum levels of lipids. The whole aortic vessels were used to show atherosclerotic lesions and the intima thickness. Serum triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol(LDL-C) were determined by commercially provided kits. The aortic atherosclerotic lesions were stained by SudanⅣ. The paraffin embedded sections of thoracic arteries and livers were stained with hematoxylin eosin. Immunohistochemistry assay was used to determine the proteins of SR-BI and PPARgamma. The mRNA expression levels of the genes in liver were detected by reverse transcription-polymerase chain reaction (RT-PCR).RESULTS: At the end of 12 weeks, serum TG, TC, HDL-C and LDL-C concentrations were markedly decreased in C57BL/6J mice supplemented with probucol, and serum TG, TC and LDL-C concentrations were significantly lowered in probucol treatment group of apoE^-/- mice. Serious lesions of the aorta in C57BL/6J mice were not observed. Probucol treatment resulted in a significant reduction of aorta lesion area in apoE^-/- mice compared with controls. Probucol contributed to a significant decrease of lipid content of the liver tissue in both C57BL/6J and apoE^-/- mice as showed by hematoxylin-eosin staining. Furthermore, RT-PCR and immunohistochemistry determination demonstrated that probucol treatment upregulated the expressions of SR-BI and PPAR_γin the mouse livers, both C57BL/6J and apoE^-/- mice.CONCLUSIONS:1. Probucol decreases the levels of serum lipids, as valued in TG, TC, LDL-C and HDL-C in mice fed with high fat/high cholesterol diet, and the lowering is more significant in C57BL/6J mice than in apoE^-/- mice.2. Probucol contributes to a significant decrease of lipid content in livers of both C57BL/6J and apoE^-/- mice, and a significant reduction of aorta lesion in apoE^-/- mice.3. Probucol upregulates the expressions of SR-BI and PPAR_γin the livers of mice fed with high fat/high cholesterol. The lipid lowering and antiatherosclerotic effects may be associated with the upregulation of SR-BI and PPAR_γexpression in livers.