Effects Of Probucol On Cholesterol-related Transporters And Inflammatory Cytokines In Hyperlipidemia Rabbits

OBJECTIVE: To investigate the effect of probucol on cholesterol-relatedtransporters and inflammatory cytokines by the establishment of hyperlipidemiarabbit model with high-fat diet.METHODS And RESULTS:36New Zealand white rabbits（weighing1.2kg~1.5kg) were randomly divided into four groups (n=9per group) as following:(1) controlgroup were fed with standard rabbit chow diet,(2) control treated group were fed withstandard rabbit chow diet supplemented with probucol,(3) high-fat diet group werefed with high-fat diet,(4) high-fat diet treated group were fed with probucol andhigh-fat diet. After7weeks, plasma total cholesterol (TC), triglyceride(TG), highdensity lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol(LDL-C) were determined by commercially enzymatic methods. Sudan Ⅳ stainingwas used to examine the aortic atherosclerotic lesions. Lipid deposition in the liver isdetected by Oil red O staining. Protein and gene expression were analyzed by Westernblot and qRT-PCR, respectively. Probucol treatment resulted in a significant reductionof atherosclerotic lesion area when compared with high fat plus probucol group.Probucol significantly decrease the serum levels of TC, LDL-C, HDL–C, TG andinflammatory cytokines when compared with high fat group. Compared to the high fatgroup, expression of ABCG5, ABCG8and SR-B1in hepatocytes, and expression ofABCG5and ABCG8in small intestines were remarkably up-regulated in the high fatplus probucol group, but it inhibit expression of ABCA1in hepatocytes. CONCLUSION: We demonstrate that probucol inhibit expression of ABCA1protein and gene in hepatocytes, up-regulate expression of ABCG5, ABCG8andSR-BI protein and gene in hepatocytes and small intestines，and decrease the serumlevels of inflammatory cytokines when compared with high fat group.