关键词: 早老素-1; 脑缺血; 阿尔茨海默病; 高脂饮食; 大鼠

Abstract: Objective To investigate the effect of pravastatin on the presenilin-1 (PS-1) expression in rathippocampus during chronic cerebrovascular insufficiency (CVI).Methods Total 36 male Wistar rats between 8 to 10 months were randomly assigned to 7 ofnormal diet group. Hyperlipidemia rats established by feeding high-fat diet were subassigned to 6of pseudo-operation group, 7 of pravastatin group, 7 of CVI group, and 9 of CVI plus pravastatingroup. After 2 months of the permanent of bilateral occlusion of both common carotid arteries, allrats were sacrificed for the serum lipid analysis and ELISA for the β amyloid (Aβ) from plasma andbrain tissue. Total cholesterol(TC), triglyceride(TG), high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C) were determined and levels of presenilin 1 inhippocampus tissues were analyzed by Western Blot.Results High-fat diet elevated the levels of TC, TG, and LDL-C. Pravastatin decreased TCalmost to the normal level, but not for TG. LDL-C could be decreased substantially. Comparedwith unchanged level of the plasma β amyloid in all groups, those hyperlipidemia rats showedmildly elevated Aβ in brain tissue. More importantly, Aβ in brain tissue of CVI rats increasedstatistically(P<0.01), and it could be downregulated by pravastatin significantly(P<0.01). WesternBlot results showed that high-fat diet caused the elevated PS-1 and pravastatin strongly inhibited itin both groups.Conclusion Pravastatin can decrease the over-produced Aβ in brain tissue as well as regulate theexpression of PS-1. So it would be effective in prevention and treatment of Alzheimer’s disease.

Key words: Presenilin-1; Cerebrovascular insufficiency; Alzheimer’s disease; High-fat diet; Rats