RESUMEN
Objective:To observe the expression levels of niemann-pick C1-like 1 (NPC1L1) and adenosine triphosphate-binding cassette transporters G8 (ABCG8) in intestine of hyperlipidemic model rats, in order to investigate the therapeutic mechanism of Shuangyu Tiaozhi decoction on hyperlipidemia. Method:A total of 40 SD rats were selected, including 8 for normal control group. The remaining 32 rats were used to establish hyperlipemic model. After modeling, the rats were randomly divided into the model group (equivalent normal saline), the high and low-dose Shuangyu Tiaozhi groups (15.6, 7.8 g·kg-1), and the Simvastatin group (4 mg·kg-1), with 8 in each group. They were given drugs by gavage for 8 weeks. The levels of total cholesterol (TC), triglyceride (TG) in serum and total cholesterol (TTC), free cholesterol (FTC) in liver of rats in each group were determined by biochemical and enzymatic methods. The morphological changes of liver were observed by hematoxylin-eosin (HE) staining, and the levels of expressions of NPC1L1, ABCG8 and liver X receptor-α (LXR-α) in intestine were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. The expression of ABCG8 protein was determined by immunohistochemistry. Result:After successful replication of the hyperlipidemia model, the blood lipid level was abnormally increased, and the liver steatosis became obvious in the model group compared with the normal control group. The expression levels of NPC1L1, LXR-α and ABCG8 increased significantly (PPα were significantly down-regulated, but ABCG8 was obviously up-regulated in a dose-dependent manner (PPPPPPConclusion:Shuangyu Tiaozhi decoction can reduce the blood lipid level of hyperlipemic rat model by reducing the absorption of cholesterol. Its mechanism may be correlated with the down-regulation of NPC1L1 expression and the up-regulation of ABCG8 expression.
RESUMEN
Objective: To investigate the hypolipidemic effects of powder of Panax notoginseng (PPN) and explore its possible mechanism. Methods: Hyperlipidemic rats model was established, and orally given three dosages of PPN for 8 weeks. The levels of serum ALT, AST, TC, TG, and LDL-C were detected. The pathological changes of liver tissues were observed by H&E staining. Gene expressions of hepatic low density lipoprotein receptor (LDLR), SIRT1, and LXR-α were measured with RT-PCR analysis. Protein expression of SREBP-2 and SCAP was determined by Western blotting. Results: Three dosages of PPN significantly decreased serum ALT, AST, TC, TG, and LDL-C levels. Histological data indicated that PPN notably reduced liver injury and hepatic steatosis in hyperlipidemic rats. In molecular study, mRNA expression of hepatic LDLR and SIRT1 was up-regulated and LXR-α gene expression was down-regulated in PPN treated rats. Additionally, PPN significantly reduced protein expression of SREBP-2 and SCAP. Conclusion: The positive effect of PPN on hyperlipidemic rats may be related to the inhibition of cholesterol synthesis of PPN through the up-regulation of SIRT1 and down-regulation of LXR-α and SCAP/SREBP-2 signaling pathway. Additionally, PPN could up-regulate hepatic LDLR mRNA expression and improve uptake of LDL-C in circulation.