Regulation of apolipoprotein A-I gene expression by ascorbic acid in scurvy-prone ODS-od/od rats.

载脂蛋白a - i （Apo a - i）是血清高密度脂蛋白（HDL）的主要载脂蛋白，它将胆固醇从外周组织转运到肝脏。我们观察到易患坏血病的ODS-od/od大鼠抗坏血酸（AsA）缺乏时血清HDL中的载脂蛋白A-I降低。在这项研究中，我们研究了AsA缺乏导致血清中低水平载脂蛋白a - i的机制。与对照组相比，asa缺乏组肝脏Apo A-I mRNA水平下降（50%），小肠Apo A-I mRNA水平下降（50%）。由于AsA缺乏不影响Apo A-I基因的转录率，因此可能需要AsA来稳定Apo A-I mRNA。此外，与对照组相比，抗坏血酸缺乏大鼠肝脏中白蛋白mRNA水平较低，接触珠蛋白mRNA水平较高，1-酸糖蛋白mRNA水平较高。包括载脂蛋白A-I mRNA在内的肝脏mRNA水平的这些变化也在急性期或炎症期观察到。目前，我们正在测定血清中白细胞介素-6的水平，白细胞介素-6是抗坏血酸缺乏患者急性期和炎症期分泌的主要细胞因子。

Apolipoprotein A-I (Apo A-I) is a major apolipoprotein of serum high density lipoprotein (HDL) , which transports cholesterol from peripheral tissues to liver. We observed that apo A-I in serum HDL was decreased in ascorbic acid (AsA) deficiency in scurvy-prone ODS-od/od rats. In this study, we examined the mechanism how AsA deficiency causes a low level Apo A-I in serum.The Apo A-I mRNA level in the liver but not in the small intestine was decreased (50%) in AsA-deficient group compared to in the control group. As AsA deficiency did not affect the transcription rate of Apo A-I gene, AsA might be required to stabilize Apo A-I mRNA.Moreover, a lower level of albumin mRNA,a higher level of haptoglobin mRNA and a higher level of 1-acid glycoprotein mRNA in the liver was observed in ascorbic acid-deficienct rats compared to in the control rats. These changes in hepatic levels of mRNA including Apo A-I mRNA are also observed in acute phase or inflammation. At present, we are measuring the serum levels of interleukin-6, which is a major cytokine secreted in acute phase and inflammation, in ascorbic acid deficiency.