RESUMO
Objective::To study the effect of evodia on lipid metabolism and low-density lipoprotein-receptor(LDL-R) mRNA expression in hyperlipidemia mice. Method::Kunming mice (n=80) were randomly divided into normal control group (n=20) and model group (n=60). Serum lipids of the model group were measured after 3 weeks.After successful modeling, the mice can be randomly divided into 5 groups (with 10 in each group): model group (equivalent normal saline), positive control group (simvastatin, 5 mg·kg-1·d-1), drug group (evodia of 5.25, 10.5, 21 mg·kg- 1·d- 1). The mice were given drugs for 3 weeks.Htoxylin-eosin(HE) staining was used to observe the liver cell structure and the change of aortic arch atherosclerosis in the mice.The enzyme linked immunosorbent assay kit was used to test the contents of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total serum adiponectin (ADPN) in serum of the mice.The expression of LDL-R mRNA in liver of each group was detected by reverse transcription-polymerase chain reaction (RT-PCR). Result::Liver HE staining showed hepatocyte swelling with steatosis in the model group, and alleviated liver steatosis in high-dose, medium-dose evodia and simvastatin groups.HE staining showed damages on the aortict arch wall in the model group, with obvious intima thickening and inflammatory cell infiltration.The intima was thickened obviously in the low-dose group, and the structure of aortic vessel wall was clear in the high-dose group.Compared with the normal group, TC, TG and HDL-C levels in serum of the model group were increased, while HDL-C level was decreased (P<0.01). Serum TC and TG levels of mice in the medium and high-dose groups decreased, whereas LDL-C and HDLl-C levels increased in low, medium and high-dose groups (P<0.05, P<0.01). Compared with the normal group, the adiponectin level in the model group was decreased, while the serum adiponectin levels in medium and high-dose groups were significantly increased (P<0.01). The LDL-R mRNA expression in the liver of mice in the model group was significantly reduced compared with the normal group (P<0.01). The LDL-R mRNA expression in medium and high-dose evodia groups was significantly increased compared with the model group (P<0.01). Conclusion::Evodia can improve the tendency of hepatic lesions and aortic atherosclerosis in hyperlipidemia mice, which may be related to the regulation of adiponectin level, the reduction of lipid content in mice and the up-regulation of LDL-R mRNA expression in mice liver.
RESUMO
Objective To investigate the effects of angiotensin Ⅱ (Ang Ⅱ) stimulating on cholesterol influx in human renal proximal tubular epithelial cells (HK-2) and the relation to low-density lipoprotein receptor (LDLr) pathway.Methods HK-2 cells were cultured and divided into the control group (incubated with serum-free medium) and Ang Ⅱ group (treated by 10-7 mol/L of Ang Ⅱ for 24 hours).The effects of Ang Ⅱ on lipid accumulation were examined by Oil red O staining and a quantitative assay of intracellular cholesterol.The expression of LDLr,sterol regulatory elementbinding protein (SREBP) cleavage activating protein (SCAP) and SREBP-2 mRNA and protein were examined by real-time PCR and Western blotting.The cotranslocation of SCAP-SREBP-2 from endoplasmic retieulum to Golgi in HK-2 cells was examined by immunofluorescent staining under confocal microscopy.Results Ang Ⅱ treatment increased intracellular lipid accumulation in HK-2 cells,which was associated with increased mRNA and protein expression of LDLr,SCAP,and SREBP-2 in HK-2 cells induced by Ang Ⅱ.Furthermore,results from confocal microscopy observation demonstrated that Ang Ⅱ increased the translocation of SCAP/SREBP-2 complex from endoplasmic reticulum to Golgi,thereby up-regulating LDLr gene transcription.Conclusion Ang Ⅱ disrupts LDLr feed-back regulation to increase cholesterol uptake and induce intracellular lipid accumulation.