Objective:To investigate the effect and molecular mechanisms of different doses of 8-hydroxy dihydroberberine(Hdber) for the treatment of hyperlipidemia in rats.Methods:A rat model of hyperlipidemia was established by feeding rats a high-fat diet for 4 weeks in 70 rats of 80 animals,and 10 rats were randomly selected as control group.The hyperlipidemic rats were then randomly divided into the following groups:a model group(MOD);a berberine group[BBR,156 mg/(kg·day)];Hdber groups,which were treated with different doses of Hdber[78,39 and 19.5 mg/(kg·day)];and a simvastatin group[SIM,4 mg/(kg·day)].The corresponding therapy was administered to the rats of each treatment via gastric tubes.Normal animals were used as a control group.The blood levels of various lipids,including total cholesterol,triglycerides,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,free fatty acid(FFA),apolipoprotein AⅠ(Apo-A Ⅰ) and apolipoprotein B(Apo-B) were examined.The protein expressions of low-density lipoprotein receptor(LDL-R),sterol regulatory element-binding protein 2(SREBP-2),3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGCR) and proprotein convertase subtilisin/kexin type 9(PCSK-9) in liver tissues were determined by Western blot analysis.Results:Compared with the control group of rats,the model group demonstrated a deteriorated blood lipid profile and exhibited increased expression levels of PCSK-9protein in their liver tissues(P<0.01).In addition,the high-fat diet decreased the expression levels of LDL-R,SREBP-2and HMGCR proteins in murine liver tissues.However,the addition of berberine or Hdber reversed the blood lipid profile changes(P<0.05 or P<0.01),decreased the expression levels of PCSK-9 proteins(P<0.01),and increased the expression levels of LDL-R proteins in the hyperlipidemic rats(P<0.01).These compounds did not significantly influence the expression levels of SREBP-2 and HMGCR proteins in the hyperlipidemic rats.Conclusions:Hdber is effective in the treatment of hyperlipidemia in rats.The therapeutic mechanisms of Hdber may be associated with increasing the expression of LDL-R protein and decreasing the expression of PCSK-9 protein in liver tissues. Objective: To investigate the effect and molecular mechanisms of different doses of 8-hydroxy dihydroberberine (Hdber) for the treatment of hyperlipidemia in rats. Methods: A rat model of hyperlipidemia was established by feeding rats a high-fat diet for 4 weeks in 70 rats of 80 animals, and 10 rats were randomly selected as control group. The hyperlipidemic rats were then randomly divided into the following groups: a model group (MOD); a berberine group [BBR, 156 mg / (kg · day)]; Hdber groups, which were treated with different doses of Hdber [78,39 and 19.5 mg / (kg · day)]; and a simvastatin group [SIM, 4 mg / (kg · day)]. The corresponding therapy was administered to the rats of each treatment via gastric tubes. Normal animals were used as a control group. The blood levels of various lipids, including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, free fatty acids (FFA), apolipoprotein AⅠ (Apo-A Ⅰ) and apolipoprotein B (Apo-B) were examined.The protein ex pressions of low-density lipoprotein receptor (LDL-R), sterol regulatory element-binding protein 2 (SREBP-2), 3-hydroxy-3- methylglutaryl coenzyme A reductase (HMGCR) and proprotein convertase subtilisin / kexin type 9 9) in liver tissues were determined by Western blot analysis. Results: Compared with the control group of rats, the model group demonstrated detertimorated blood lipid profile and showed increased expression levels of PCSK-9 protein in their liver tissues (P <0.01). In addition, the high-fat diet decreased the expression levels of LDL-R, SREBP-2 and HMGCR proteins in murine liver tissues. However, the addition of berberine or Hdbl reversed the blood lipid profile changes (P <0.05 or P <0.01) , decreased the expression levels of PCSK-9 proteins (P <0.01), and increased the expression levels of LDL-R proteins in the hyperlipidemic rats (P <0.01). These compounds did not significantly affect the expression levels of SREBP-2 and HMGCR proteins in the hyperlipidemic rats. Conclusions: Hdber is ef fectivein the treatment of hyperlipidemia in rats. The therapeutic mechanisms of Hdber may be associated with increasing the expression of LDL-R protein and decreasing the expression of PCSK-9 protein in liver tissues.