| Objective:Hyperlipidemia(HLP) is due to confusion of synthesis in the blood. The plasma lipoprotein is abnormal and the blood lipid is heighten. It belongs to "phlegm" and "blood stasis" in the traditinal Chinese medicine and is on the rise. Modern pharmacology and clinical studies also indicated that Alismatis Rhizoma Decoction (ARD) is decoction has a significant role in regulating blood cholesterol. The existing study demonstrated that the anti-hyperlipidemia effect of ARD is to interfer exogenous cholesterol absorption and endogenous cholesterol metabolic, and anti-lipid peroxidation. It also embodies characteristics of ARD like various ways and targets for cholesterol metabolism. However, it is preliminary to study the anti-hyperlipidemia effect of ARD in molecular biology research. There is little information available about the cholesterol-lowering effect of ARD and the mechanism of the effect works. The lipid profile was taken as the major markers of hypercholesterolaemia in our study. Accordingly, serum total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL-C), and liver TC, TG were among the parameters investigated. Meanwhile, the effects of ARD and its component TCMs AR and AMR on the liver toxicity were also examined. Specifically, we assessed influence of ARD and its component TCMs AR and AMR on the three key hepatic cholesterol metabolism genes for 3-hydroxy-3-methylglutharyl-coenzyme A reductase, sterol regulatory element binding factor-2 (SREBF-2) and cholesterol-7a1pha-hydroxylase (CYP7α1) in order to find the potential molecular mechanism by which ARD modulated lipid profiles.Methods:sixty mice were acclimatized for 7 days before being randomly divided into 2 groups. The first group had 8 mice and continued to receive a regular diet as the control group. The rest mice were transferred to a hypercholesterolemic diet. (1) Control (C) group:receive a regular diet, intragastric administration with physiologic saline. (2) Hyperlipidemia Model (HM) group:receive a high-fat diet, intragastric administration with physiologic saline. (3) Simvastatin (P) group:receive a high-fat diet, intragastric administration with 6.7mg·kg-1 Simvastatin. (4) Alismatis Rhizoma (AR) group:receive a high-fat diet, intragastric administration with 2g·ml-1 Alismatis Rhizoma. (5) Atractylodis Macrocephalae Rhizoma (AMR) group:receive a high-fat diet, intragastric administration with 2g·ml-1AMR. (6) Alismatis Rhizoma Decoction (ARD) group:receive a high-fat diet, intragastric administration with 2g·ml-1 ARD. The body weight and food consumption were recorded weekly. The content of TC, TG, HDL-C and activities of ALT and AST in serum were measured respectively. The organ coefficient was also calculated. The livers were used to extract RNA and study the histological changes of livers. Results:1. The anti-hyperlipidemia of AR and ARD in mice.Compared with model groups, AR and ARD groups all have lower serum TC and TG levels, higher serum HDL-C level, lower activity of serum ALT and AST, lower liver coefficient;Compared with AR group, ARD group have lower weight as well as lower liver coefficient.2. The effect of AR and ARD on the relative quantity of cholesterol related genes.Compared with control group, induction of HMG-CoA reductase and SREBF-2 genes were taken place on hyperlipidemia mice. Compared with model groups, AR and ARD down regulated HMG-CoA reductase and SREBF-2 mRNAs, but had no significant effect on CYP7AmRNA. AMR had no significant effect on HMG-CoA reductase, SREBF-2 and CYP7α1 mRNAs.Conclusions:1. The combination of AR and AMR was enable to enhance the potency of anti-hyperlipidemia effect and the formula of ARD was reasonable.2. The mechanism of anti-hyperlipidemia effect for AR and ARD was probably down-regulation of HMG-CoA reductase and SREBF-2 mRNAs.SUBJECT WORDS:Alismatis Rhizoma Decoction; hyperlipidemia; synergistic effect; Cholesterol related genes... |
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