衰老对大鼠过氧化体增殖物激活受体α表达的影响与脂质代谢的关系

Effects of aging on the expression of peroxisome proliferator-activated receptor α and the relation to lipid metabolism

目的 观察衰老对过氧化体增殖物激活受体α和目标基因脂蛋白脂酶、载脂蛋白CⅢ组织表达的影响 ,从而探讨衰老过程中出现脂质代谢异常的可能机制。方法 雄性SD年轻大鼠 (4～ 6周龄 ) 16只和老年大鼠 (2 4月龄 )16只 ,随机分为对照组和给药组 (非诺贝特喂养 2周 ) ,测定血清中甘油三酯 (TG)和总胆固醇 (TC)水平 ,采用半定量逆转录 聚合酶链反应法检测过氧化体增殖物激活受体α及脂蛋白脂酶、载脂蛋白CⅢmRNA水平 ,用Western印记法检测过氧化体增殖物激活受体α蛋白表达情况。结果 与年轻对照组比较 ,老年对照组的血脂中TG和TC水平升高 ,过氧化体增殖物激活受体αmRNA及过氧化体增殖物激活受体α蛋白表达随年龄增长而减少 ,同时脂蛋白脂酶、载脂蛋白CⅢ也受年龄的影响。给药组与对照组比较 ,给药后老年对照组TG下降。非诺贝特对不同年龄组过氧化体增殖物激活受体α的表达均无影响 ,但可影响脂蛋白脂酶、载脂蛋白CⅢ的表达。结论 衰老过程中过氧化体增殖物激活受体α表达减少可能与老年脂质代谢异常有关。

Objectives To investigate the effects of aging on peroxisome proliferator-activated receptor α(PPARα) and lipoprotein lipase(LPL),apolipoprotein CⅢ(ApoCⅢ)expression and explore the molecular mechanism of lipid metabolism during aging.Methods Two groups of SD rats were used to estimate the lipid level of young(4～6 weeks) and aged(24 months) groups,and the rats were divided into two groups:control and treated groups(fenofibrate for 2 weeks) at random.The levels of liver PPARα and LPL、ApoCⅢ mRNA were measured by reverse transcription-polymerase chain reaction (RT-PCR) and PPARα protein were determined by Western blotting respectively.Results The triglyceride(TG) and total cholesterol(TC) levels of the aged group were significantly increased as compared with the young group.The PPARα mRNA and protein level of the aged group were significantly decreased as compared with the young group.The LPL and apoCⅢ mRNA were markedly changed with aging.Fenofibrate reduced plasma TG and TC in aged-treated group.Fenofibrate had no effect on the expression of PPARα in these groups,but had effects on expression of LPL and ApoCⅢ.Conclusion The mechanism of lipid metabolism dysfunction during aging is probably associated with the decreased expression of PPARα.