Sesamin Rats With High Blood Lipids Cholesterol Metabolism And Related Gene Expression

Objective:To determine the effect of sesamin on hepatic gene expression related to cholesterol metabolism, and to explore molecular mechanisms involved in lipid metabolism in rats.Methods:Rats were allowed 1 week to adapt to their environment before being used for experiments.40 male SD rats were randomly divided into normal control group, high fat control and three sesamin groups according to the initial serum cholesterol and body weight. The rats in each group were 8 individuals. Rats in sesamin intervention groups were treated with sesamin 20, 40,80mg/kg·d-1 by intragastric administration, respectively. Rats were executed on the end of 9 weeks and indexes as follow were checked:①serum total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), apolipoprotein A I, B (ApoA I and ApoB) levels and calculated AI, R-CHD, LCI, and HDL/TC value.②liver indicators:lipoprotein lipase (LPL) and hepatic lipase (HL).③molecular target: 3-hydroxy-3-methylglutarycoenzyme (HMG-COA) reductase, low density lipoprotein receptor (LDL-R), cholesterol 7a hydroxylase (CYP7A1).Results:1. After three weeks, the level of serum cholesterol in model group was significantly higher than that of normal control group (P<0.01). Compared with model group, the level of serum cholesterol in the sesamin intervention groups was significantly decreased at the end of 9 weeks (P>0.05).2. The level of serum high density lipoprotein-cholesterol in model group was lower than those of control group and the intervention groups (P＜0.05). Level of serum low density lipoprotein-cholesterol was higher than those in control group, middle and high dose intervention groups (P<0.05). Compared with model group, serum triglyceride in intervention group decreased, but the difference was not significant (P>0.05).3. The levels of AI, R-CHD and LCI in model group was higher than the normal control group and nutrition intervention group (P＜0.05). However, HDL/TC in model group was lower than those of control group and the nutrition intervention groups (P<0.05).4. Level of apolipoprotein A I in serum in model group was lower than those of control group and the nutrition intervention groups (P<0.01). Compared with model group, serum ApoB of nutrition intervention groups decreased, but the difference was not significantly (P>0.05).5. Liver lipoprotein lipase was lower than those of control group and high dose intervention group (P＜0.01). Compared with model group, liver hepatic lipase level in the intervention groups increased, but the difference was not statistically significant (P>0.05).6. The mRNA expression levels of 3-hydroxy-3-methylglutarycoenzyme reductase in liver in model group were markedly higher than those of normal control group and nutrition intervention groups (P<0.01). Low density lipoprotein receptor and cholesterol 7αhydroxylase of model group level was lower than the control group and the nutrition intervention group (P<0.01).Conclusion:The levels of total cholesterol, low density lipoprotein-cholesterol of hypercholesterolemia could be significantly decreased and the level of high density lipoprotein-cholesterol increased by sesamin. Following mechanisms may be involved in:1) inhibiting cholesterol synthesis rate-limiting enzyme (3-hydroxy-3-methylglutarycoenzyme reductase) expression, limiting synthesis of endogenous cholesterol; 2) increasing serum apolipoprotein AI, the liver activity of Liver lipoprotein lipase and cholesterol 7αhydroxylase mRNA.