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Epidemiological and biochemical studies strongly implicate a role for cholesterol in the pathogenesis of Alzheimers disease(AD).Even though its confirmed that cholesterol cannot pass the blood-brain-barrier,treatment of rats with dietary cholesterol caused significant effects on impaired learning and memory.We have suggested that oxysterol especially 27-hydrocholesterol plays a potential role in p-amyloid peptides production and accumulation during AD progression.To investigate the mechanisms of dietary cholesterol and 27-OHC on learning and memory ability impairment,male Sprague-Dawley rats were fed with a cholesterol-rich diet with or without inhibitor of synthetase of 27-OHC(anastrozole)injected.We determined the levels of total cholesterol and oxysterols(27-OHC,24S-OHC,7α-OHC,7β-OHC)in plasma,apolipoprotein(ApoA,ApoB)and high-density-lipoprotein cholesterol as well as low-density-lipoprotein cholesterol in plasma or brain of rats,cholesterol metabolic enzymes in liver(CYP27A1,CYP7A1)or in brain(CYP46A1,CYP7B1),lysosomal function related protein(cathepsin B,cathepsin D,acid phosphatase)and β-amyloid peptides(Aβ1-40,Aβ1-42)in brain.Results showed that cholesterol diet increased the levels of cholesterol and 27-OHC in plasma,increased levels of LDL-C and ApoB in plasma or in brain,decreased level of HDL-C in plasma,upregulated the expression of CYP27A1 and CYP7A1 in livers,altered lysosomal function and increased Aβ in brain.This study indicated that the mechanisms of dietary cholesterol on cognition may involve in cholesterol metabolism and lysosome function with the increase of plasma 27-OHC,resulting in β-amyloid(Aβ)formation and accumulation.