在慢性肾衰竭大鼠模型中，过氧化物酶体增殖物激活受体α基因表达降低与血脂异常有关。
Decreased peroxisome proliferator-activated receptor alpha gene expression is associated with dyslipidemia in a rat model of chronic renal failure.
作者信息
Mori Yusaku, Hirano Tsutomu, Nagashima Masaharu, Shiraishi Yuji, Fukui Tomoyasu, Adachi Mitsuru
机构信息
First Department of Internal Medicine, Showa University, School of Medicine, Tokyo, Japan.
出版信息
Metabolism. 2007 Dec;56(12):1714-8. doi: 10.1016/j.metabol.2007.07.016.
The transcription factor peroxisome proliferator-activated receptor (PPAR) alpha plays an important role in lipid homeostasis. In this study, we examined whether the down-regulation of PPAR-alpha gene expression is associated with dyslipidemia in a rat model of chronic renal failure (CRF). Rats with laboratory-induced uremia by 5/6 nephrectomy were bled at 2 weeks and 10 weeks after the nephrectomy to produce conditions. For the sake of convenience, the rats observed at postoperative week 2 were defined as acute renal failure (ARF) and those observed at week 10 were defined as CRF. Lipids in lipoprotein fractions were measured by high-performance liquid chromatography. The abundance of PPAR-alpha messenger RNA (mRNA) in the liver was measured by reverse transcriptase-polymerase chain reaction. Serum creatinine and blood urea nitrogen levels rose with the progression of renal failure, but the total protein levels remained constant. Serum triglyceride in ARF rats remained unchanged from the level in sham-operated control rats, whereas that in CRF rats was 66% higher than the control level. Serum cholesterol was elevated 1.5-fold in ARF rats and 2-fold in CRF rats compared with the sham-operated counterparts. As with triglyceride, very low-density lipoprotein remained unchanged in ARF rats but rose substantially in CRF rats. All of the major lipoprotein fractions were elevated in CRF rats. These lipid and lipoprotein changes were significantly associated with creatinine and blood urea nitrogen levels. The PPAR-alpha mRNA expression in the liver was unchanged in ARF rats but was 44% lower in CRF rats. The PPAR-alpha mRNA expression was inversely correlated with serum creatinine and lipids in the overall rats. Our results indicate that PPAR-alpha mRNA expression is down-regulated in the liver of CRF rats and that this down-regulation may play a crucial role in the development of dyslipidemia.
转录因子过氧化物酶体增殖物激活受体（PPAR）α在脂质稳态中发挥重要作用。在本研究中，我们检测了在慢性肾衰竭（CRF）大鼠模型中，PPAR-α基因表达下调是否与血脂异常有关。通过5/6肾切除诱导实验性尿毒症的大鼠在肾切除术后2周和10周采血以建立相应状态。为方便起见，将术后第2周观察的大鼠定义为急性肾衰竭（ARF），第10周观察的大鼠定义为CRF。采用高效液相色谱法测定脂蛋白组分中的脂质。通过逆转录聚合酶链反应测定肝脏中PPAR-α信使核糖核酸（mRNA）的丰度。血清肌酐和血尿素氮水平随肾衰竭进展而升高，但总蛋白水平保持不变。ARF大鼠的血清甘油三酯水平与假手术对照大鼠相比无变化，而CRF大鼠的血清甘油三酯水平比对照水平高66%。与假手术组相比，ARF大鼠的血清胆固醇升高1.5倍，CRF大鼠升高2倍。与甘油三酯一样，ARF大鼠的极低密度脂蛋白水平无变化，但CRF大鼠显著升高。CRF大鼠所有主要脂蛋白组分均升高。这些脂质和脂蛋白变化与肌酐和血尿素氮水平显著相关。ARF大鼠肝脏中的PPAR-α mRNA表达无变化，但CRF大鼠降低44%。在所有大鼠中，PPAR-α mRNA表达与血清肌酐和脂质呈负相关。我们的结果表明，CRF大鼠肝脏中PPAR-α mRNA表达下调，这种下调可能在血脂异常的发生中起关键作用。
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