Abstract:

Objective To explore the effect of the Jianpi Huayu Qutan method on the dyslipidemia in the rats and to elucidate its molecular mechanism based on apolipoprotein A-Ⅰ（apoA-Ⅰ）/ adenosine monophosphate activated protein kinase （AMPK） / carnitine palmitoyltransferase Ⅰ A（CPT1A） signaling pathway. Methods A total of 32 rats were randomly divided into blank control group， model group， simvastatin group （given 1.575 mg·kg^－1·d^－1 simvastatin） and Huayu Qutan Prescription（HYQTP） group （given 13.846 mg·kg^－1·d^－1 HYQTP drug）， and there were 8 rats in each group. The rats in blank control group were given normal diet，and the rats in model group， simvastatin group and HYQTP group were given high-fat diet to establish the hyperlipidemia rat models. After 8 weeks， the rats in simvastatin group and HYQTP group were given drugs by gavage； the rats in blank control group and model group were given the same volume of normal saline. The levels of total cholesterol （TC）， triglycerides （TG）， low density lipoprotein cholesterol （LDL-c） and high density lipoprotein cholesterol （HDL-c） in serum of the rats in various groups were detected by automatic biochemical analyzer；HE staining was used to observe the pathomorphology of liver tissue of the rats in various groups； Oil red O staining was used to observe the lipid deposition in liver tissue of the rats in various group； the levels of TG in liver tissue of the rats in various groups were detected；ELISA method was used to detect the levels of apoA-Ⅰ in liver tissue of the rats in various groups；real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of apoA-Ⅰ， scavenger receptor class B type 1 （SR-B1）， and CPT1A mRNA in liver tissue of the rats in various groups；Western blotting method was used to detect the expression levels of SR-B1， phosphorylated AMPK （p-AMPK）and CPT1A proteins in liver tissue of the rats in various groups. Results Compared with blank control group， the levels of serum TC， TG，and LDL-c of the rats in model group were increased （P<0.05）， and the level of serum HDL-c was decreased （P<0.05）； the level of TG in liver tissue of the rats was increased （P<0.05）； the hepatocytes showed obvious swelling and increased volume， and the obvious red lipid droplet distribution could be seen； the expression levels of apoA-Ⅰ，SR-B1， and CPT1A mRNA and protein were decreased （P<0.05）， and the ratio of p-AMPK/AMPK was decreased （P<0.05）；compared with model group， the levels of serum TC， TG，and LDL-c in liver tissue of the rats in simvastatin group and HYQTP group were decreased （P<0.05）， and the level of HDL-c was increased （P<0.05），the level of TG in liver tissue was decreased （P<0.05）；the swelling of hepatocytes was obviously reduced，and the distribution of lipid droplets was decreased obviously； the expression levels of apoA-Ⅰ， SR-B1， and CPT1A mRNA and proteins were increased （P<0.05）， and the ratio of p-AMPK/AMPK was increased （P<0.05）. Conclusion The Jianpi Huayu Qutan method can improve the dyslipidemia and reduce the liver damage and lipid deposition of the hyperlipidemia rats， and its mechanism may be related to regulating the apoA-Ⅰ/AMPK/CPT1A signaling pathway and promoting fatty acid β oxidation in the rats.

Key words: Dyslipidemia, Fatty acid β oxidation, Apolipoprotein A-Ⅰ, Adenosine monophosphate activated protein kinase, Carnitine palmitoy ltransferase ⅠA