关键词: 山楂原花青素；高脂血症；腺苷酸激活蛋白激酶；固醇调节元件结合蛋白

Abstract: Objective: To investigate the effect of hawthorn procyanidins (HPC) on lipid metabolism and its mechanism by regulating the AMP-activated protein kinase/sterol regulatory element binding protein-1c (AMPK/SREBP-1c) signaling pathway. Methods: Sixty rats were randomly divided into six groups (n = 10) blank control (BC), hyperlipidemia model (HM), low-, medium-, and high-dose HPC (HPC-LD, HPC-MD, and HPC-HD) and fenofibrate positive control (FP). The contents of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in the serum and liver homogenate were measured by commercial kits. Hematoxylin eosin (HE) staining was used to observe hepatic histopathological changes. The mRNA expression levels of AMPK, SREBP-1c, glycerol-3-phosphate acyltransferase-1 (GPAT1), acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), carnitine palmitoyltransterase-1 (CPT1) and peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) in the liver were measured by quantitative real-time polymerase chain reaction (PCR). Western blotting was used to detect the protein expression of p-AMPK, SREBP-1c, GPAT1, ACC, FAS, CPT1 and PGC-1α in the liver. Results: After seven weeks of feeding on a high-fat diet, body mass, liver mass and liver index significantly increased compared with the control group fed on a basal diet (P < 0.05 or < 0.01). Compared with the HM group, the contents of TG, TC and LDL-C in serum and liver homogenate in the HPC-HD and FP groups significantly decreased, and the content of HDL-C significantly increased (P < 0.01); the effect of HPC on lipid content in serum and liver homogenate was dose-dependent. After prophylactic intervention with HPC, the steatosis of hepatocytes was gradually improved with an increase in the dosage of HPC. Compared with the HM group, the AMPK mRNA expression and p-AMPK protein expression in liver tissues in the HPC-HD and FP groups significantly increased (P < 0.01), and the mRNA and protein expression of SREBP-1c, GPAT1, ACC and FAS significantly decreased (P < 0.01), and the mRNA and protein expression of CPT1 and PGC-1α significantly increased in the liver (P < 0.01). Conclusion: HPC can effectively improve lipid metabolism in hyperlipidemic rats, which may be related to the regulation of the AMPK/SREBP-1c signaling pathway.

Key words: hawthorn procyanidins; hyperlipidemia; AMP-activated protein kinase (AMPK); sterol regulatory element binding protein-1c (SREBP-1c)