Abstract
Objective: This study investigated into the ef-fect of lycopene on expression of APP, bax and bcl-2 in hippocampal CA1 region of rats with hyperlipidemia. Methods: By total cholesterol (TC) and body weight, 48 adult male SD rats were randomized into six groups, a normal control group, fed with basic feed; a high-fat model group, fed with high-fat feed; a positive drug control group, fed with high-fat feed and administrated with fluvastatin sodium at a dose of 10 mg?kg?bw-1?d-1 by gastric perfusion; and lycopene groups at three dose levels, fed with high-fat feed and administrated with lycopene at doses of 11, 22 and 44 mg?kg?bw-1?d-1 respec-tively also by gastric perfusion. Caudal venous blood samples of rats in all groups were taken at week 0, week 1 and week 3 after the experiment started so as to assay TC, TG, LDL-C and HDL-C; at the end of the experiment, rat brains were taken and sections of the hippocampal CA1 re-gion were prepared. Expression of APP, bax and bcl-2 in the CA1 region was determined by im-munohistochemical methods and morphologi-cal examination was carried out. Results: One week after fed with high-fat feed, models of hy-perlipidemia rats were established; at the end of experiment, hippocampal APP and bax expres-sion was enhanced while bcl-2 expression was significantly weakened (p<0.05); to rats with hyperlipidemia, both lycopene and fluvastatin sodium could reduce TC, TG and LDL-C, inhibit expression of hippocampal APP and bax and promote expression of bcl-2 (p<0.05). Conclu- sion: Lycopene down-regulates the expression of bax and up-regulates that of bcl-2 mainly by reducing serum TC and LDL-C and weakening expression of APP in the hippocampal CA1 re-gion of rats with hyperlipidemia, thereby main-taining normal morphology of hippocampal neurons and facilitating the protection of the brain.
Highlights
Lycopene is a potent singlet oxygen scavenger and has the effect of preventing free radical injuries
Findings in this study showed that hyperlipidemia could lead to excessive expression of Amyloid precursor protein (APP) and bax in hippocampal CA1 region of rats and their expressions were positively correlated, where Spearman’s rho was 0.774 and P was 0.000; bcl-2 expression was reduced and was in negative correlation with APP expression, where Spearman’s rho was -0.737 and P values was 0.000; bcl-2/bax ratio decreased and was significantly lower than that of the normal control group (P
Hyperlipidemia is closely related to the occurrence of coronary heart diseases, myocardial infarction, hyper tension, diabetes mellitus, apoplexy, etc. and poses a risk of Alzheimer disease (AD)
Summary
Lycopene is a potent singlet oxygen scavenger and has the effect of preventing free radical injuries. Studies have shown that it has many important bioactivities, e.g., quenching singlet oxygen, eliminating reactive oxygen species, blocking lipid peroxidation, suppressing cell reproduction, reinforcing immunity, and inducing gap junction intercellular communication [1,2,3,4]. Both epidemiological and laboratorial studies suggest that lycopene, a powerful antioxidant agent, can reduce the risk of cardiovascular diseases [5,6]. Blood cholesterol increase may directly lead to neuronal degeneration related to cognitive function. The biological mechanism [9] may be that blood cholesterol increase affects APP metabolism of neurons
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