Investigation Of The Anti-Atherosclerpsis Mechanism Of Phlorizin On High Cholesterol Hamsters

Phlorizin, a kind of natural ployphenols, has been used for pathological studies for over one hundred years. Hamsters fed a high fat and high cholesterol diet were used to build a hypercholesterolemia and oxidative stress model to study the anti-atherosclersis role of phlorizin. In the experiment,36 hamsters were randomly divided into a control group, 0.3%,0.6% and 0.9% phlorizin groups. Lipid levels, antioxidant enzyme activity were edtected; liver cholesterol levels and fecal sterols excretion were measured by gas chromatography; fluorescence quantitative PCR (RT-PCR) was used to detect cholesterol metabolism and antioxidant related genes expression in liver and small intestine; cholesterol regulation and antioxidant-related protein expression levels in liver were detected with western blot assay.Phlorizin could reduce serum total cholesterol (TC) and triglycerides (TG) levels and increased high-density lipoprotein cholesterol (HDL-C) levels; phlorizin could lower liver cholesterol and increase fecal steroid excretion with phlorizin increased. RT-PCR results showed that phlorizin raised liver LDL receptor (LDL-R), liver X receptor (LXRa), cholesterol 7-hydroxylase (CYP7A1) gene, while reduced 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA-R) gene expression. Western blot analysis showed phlorizin inhibition of liver HMGCR protein levels, and increased the expression levels of CYP7A1 and LXRa. Phlorizin inhibited small intestine showed HMG-CoA-R, NPC1L1, acetyl coenzyme A acetyltransferase (ACAT2), microsomal triglyceride transfer protein (MTP) mRNA expression, and incresed ABCG5/8 expression.The results of antioxidant enzyme activity assay showed that serum, heart, kidney and liver SOD, GSH-Px, CAT enzyme activity were increased significantly and the content of MDA decreased with phloridzin supplemented. RT-PCR results showed phlorizin increased superoxide dismutase (CuZn-SOD, Mn-SOD), glutathione peroxidase (GSH-Px), peroxide catalase (CAT), heme oxygenase 1 (HO-1), nuclear factor E2-related factor 2 (Nrf2) mRNA expression in liver. Westernblot test results showed that phlorizin elevated Mn-SOD, HO-1 and CAT protein expression levels.The mechanism underlying the anti-atherosclerosis of phlorizin was mediated most likely through the regulation of cholesterol-metabolism and antioxidative genes expression in hamsters.