Effects of gypenosides on PCSK9 gene expression and blood lipids lowered by simvastatin / 中国病理生理杂志

ABSTRACT

AIM:To explore the effect of gypenosides ( GPs) on PCSK9 gene expression in hyperlipidemic rat liver and the blood lipids lowered by simvastatin .METHODS: Healthy male SD rats ( n=60 ) were randomized into 5 groupsnormal control group , hyperlipidemic model group , simvastatin group , GPs group and GPs combined with simvasta-tin group ( combined group ) .The rats in all groups were fed high-fat diet except normal control group which were fed with ordinary diet.The rats in control group and hyperlipidemic model group were gavaged with 0.3%CMC-Na every day.The rats in GPs group were gavaged with GPs at 160 mg? kg-1? d-1 .The rats in simvastatin group were gavaged with simvas-tatin at 5 mg? kg-1? d-1 .The rats in combined group were gavaged with GPs and simvastatin .The experiment lasted for 8 weeks.The rats were anesthetized with chloral hydrate , and abdominal arterial blood samples were collected to detect the total cholesterol ( TC) , triglyceride ( TG) , low-density lipoprotein cholesterol ( LDL-C) and high-density lipoprotein cho-lesterol ( HDL-C) .The body weight and the wet weight of the livers were measured , and the liver index was calculated . The pathological changes of the livers were observed under microscope with HE staining .The expression of PCSK9 and low-density lipoprotein receptor ( LDLR) at mRNA and protein levels was determined by real-time PCR and Western blot .RE-SULTSThe model of hyperlipidemia rats was established successfully .Compared with model group , the levels of TC , TG and LDL-C in simvastatin group, GPs group and combined group were obviously decreased (P<0.05), and the HDL-C levels were obviously upregulated (P<0.05).Compared with model group, the liver indexes in simvastatin group, GPs group and combined group were obviously decreased (P<0.05).The pathological changes of the liver tissues showed that hepatic adipose appeared in model group , and that in simvastatin group and GPs group had different degrees of relief , espe-cially in combined group .Compared with model group , the mRNA expression levels of PCSK 9 and LDLR in simvastatin group were obviously increased , while the mRNA expression levels of PCSK 9 in GPs group and combined group were obvi-ously decreased (P<0.05), and the mRNA expression of LDLR in combined group was obviously increased (P<0.05). Compared with model group , the protein expression of PCSK 9 and LDLR in simvastatin group was obviously increased , while the protein expression levels of PCSK 9 in GPs group and combined group were obviously reduced , and the LDLR pro-tein levels were obviously increased (P<0.05).CONCLUSION:Gypenosides inhibit the expression of PCSK9 and in-crease the expression of LDLR in the liver .The combination of gypenosides and simvastatin promotes the lipid-lowering effect of simvastatin and attenuates hepatic steatosis , which may be related to inhibiting the expression of PCSK 9 in the liv-er.