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Age-related decrease in expression of peroxisome proliferator-activated receptor α and its effects on development of dyslipidemia

查看全文 作　　者：YEPing WANGZhao-jun ZHANGXiu-jin ZHAOYa-[1]li 高影响力作者 机构地区：[1]DepartmentofGeriatricCardiology,ChinesePLAGeneralHospital,Beijing100853,China高影响力机构 出　　处：《Chinese Medical Journal》索引2005年第13期,共6页高影响力期刊 基　　金：ThisstudywassupportedbyagrantfromNational'973'Foundation(No G2000057007) 摘　　要：Background Ageing is associated with increased incidence of dyslipidemia. To investigate potential molecular mechanisms, the effects of age and fibrate administration on peroxisome proliferator-activated receptor α(PPARα) expression in livers of young and old rats were studied.Methods A total of 16 young (2-month-old) and 16 old rats (24-month-old) were randomly assigned to a control group and fenofibrate group (fenofibrate in a total therapeutic dosage of 0.5% in ratio to each treated rat weight in 14 days). RT-PCR was applied to evaluate hepatic mRNA expression of PPARα and its target genes. Western blotting was used to determine PPARα protein level in liver tissue. Results When compared with 2-month-old rats, the liver tissue from 24-month-old rats showed reduced expression of PPARα mRNA (52%, P <0.05) and protein (109%, P <0.01). Consequently, the mRNA levels of PPAR target genes, LPL, ACO, ACS and CPT-1 were markedly lowered by 19%, 8%, 13% and 9% respectively, and apoCIII increased by 24% in livers from 24-month-old rats, compared with values obtained from 2-month-old rats ( P <0.05). Fenofibrate therapy significantly lowered plasma triglyceride and total cholesterol levels in old rats, accompanied with improvement in hepatic expression of genes, including LPL, ACO, ACS, CPT-1 and apoCIII, but no change was found in PPARα expression in livers from either 24-month or 2-month-old rats. Conclusions The decrease in the hepatic PPARα expression is probably directly related to the lipid metabolic disturbances observed in old animals. The beneficial effects of fenofibrate administration in old rats suggests that fibrates may be useful for treating lipid disturbances in old people. 关 键 词：年龄 过氧物酶体 酶活性 脂质代谢 药物治疗
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