【摘要】 目的研究血胆固醇(TC)对脑TC及脑β-淀粉样蛋白(Aβ)生成的影响。方法给高TC血症的W istar大鼠饲喂考来烯胺和邻苯二甲酸二异辛酯(d iethylhexyl phthalate,DEHP)促进胆汁酸的合成,降低其血TC后,测定其脑TC及Aβ的含量;以测定脑羟甲基戊二酰辅酶A还原酶HMG-COAR)和脑TC 24S-羟化酶(CYP46)的mRNA表达水平,反映脑TC的合成水平和转出水平。结果高TC血症大鼠脑Aβ含量明显增高(P<0.05),脑TC以及脑HMG-COAR和CYP46的mRNA表达水平未变;考来烯胺饮食组大鼠血TC水平明显降低(P<0.01),脑中Aβ含量和对照组一样保持在低水平,脑TC的含量有增高趋势,HMG-COAR mRNA表达增加(P<0.05),CYP46 mRNA表达无变化;DEHP饮食组血TC及脑中的Aβ无显著变化,脑TC的含量明显增高(P<0.05),脑HMG-COAR mRNA表达增加(P<0.05),CYP46 mRNA表达降低(P<0.01)。结论脑TC的含量不受血TC的直接影响,而与其自身代谢有关;整体动物脑Aβ生成量增加与脑TC浓度无关。更多还原

【Abstract】 Objective To study effect of serum cholesterol on brain cholesterol and β-amyloid peptide(Aβ).Methods Male Wistar rats with hypercholesterolemia were fed with Diethylhexyl phthalate(DEHP) or cholestyamine in order to promote synthesis of bile acid and reduce level of serum cholesterol.Cholesterol,Aβ content and expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) and cholesterol 24S-hydroxylase(CYP46) in brain,which reflect synthesis and export of cholesterol in brain,were assayed.Results There was an increase of content of Aβ in brain of rat with hypercholesterolemia(P<0.05),the expression of HMGR and CYP46 mRNA,and cholesterol level of brain did not significantly change.In the cholestyamine diet group,the content of serum cholesterol obviously reduced(P<0.01),the contents of brain Aβ did not change,the HMGR mRNA expression became higher(P<0.05),the expression of CYP46 mRNA had no change,the content of brain cholesterol just tended to go up.In the DEHP diet group,the level of serum cholesterol and brain Aβ did not change,the content of brain cholesterol increased(P<0.05),the expression of CYP46 mRNA decreased greatly(P<0.01),the expression of HMGR mRNA increased(P<0.05).Conclusions The level of brain cholesterol could not be modulated by serum cholesterol,depending on metabolism itself.There is no relationship between the generation of Aβ and cholesterol concentration in brain in vivo.更多还原