ABSTRACT
Aim To investigate the effect of intestinal cholesterol absorption inhibitor Ezetimibe on lipid accumulation in RAW264.7 cells and identify the underlying mechanism.Method RAW264.7 cells were pretreated with the indicated concentrations of Ezetimibe (0,0.003,0.01 and 0.03 mol·L~(-1))for 24 hours or pretreated with the optimal concentration(0.03 mol·L~(-1))of Ezetimibe for different periods (0,6,12 and 24 h),followed by incubation with 50 mg·L~(-1) oxLDL for 24 hours,then the number of intracellular lipid droplets and lipid content were measured by using oil red O staining and HPLC; the expression of NPC1L1 was measured by Western blot.Results Pretreatment with indicated concentrations of Ezetimibe caused a concentration-dependent inhibition of intracellular lipid accumulation;pretreatment with 0.03 mol·L~(-1) Ezetimibe caused a time-dependent inhibition of intracellular lipid accumulation.It was noted that pretreatment with 0.03 mol·L~(-1) Ezetimibe for 24 hours inhibited CE by about 47%+0.1% compared with control group(oxLDL alone).Immunoblotting results showed that NPC1L1 was expressed in RAW264.7 cells and it was down-regulated after Ezetimibe treatment.Conclusions Ezetimibe causes concentration-dependent and time-dependent inhibition of lipid accumulation in RAW264.7 cells;it also reduces NPC1L1 expression in RAW264.7 cells.
ABSTRACT
AIM To investigate the relationship between the prevention of probucol against restenosis and functional vascular remodeling after percutaneous transluminal angioplasty(PTA) in rabbits. METHODS New Zealand rabbit thoracic aorta atherosclerosis was induced by 3 5 F balloon catheter injury following a 4 week feeding of high cholesterol diet, and percutaneous transluminal angioplasty(PTA) was performed by using 3 5 F ballon catheter. Probucol(1 g?d -1 ) or vitamin E(400 mg?d -1 ) was administrated one week before PTA. Two weeks after PTA, lumen area,neointima area(NEA),medial area(MA) and NEA/MA were analyzed by computerimage system.The relaxation response of restenotic arteries to acetylcholine and the contractive response to norepinephrine, potassium chloride and serotonin of thoracic aorta rings were measured by bioassay. Nitric oxide of serum was measured by means of biochemical assay.RESULTS After two weeks of PTA, probucol increased lumen area and decreased neointima area significantly. The relaxation response of restenotic arteries to acetylcholine was significantly lower than that of normal arteries〔relaxation percent to acetylcholine (1 ?mol?L -1 ):(18 4?4 0)% vs (63 5?6 4)%, P