Ikeda S, Horio F, Kakinuma A
Laboratory of Nutritional Biochemistry, Department of Applied Biological Sciences, School of Agricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
J Nutr. 1998 May;128(5):832-8. doi: 10.1093/jn/128.5.832.
The ODS rat (genotype od/od), which has a hereditary defect in ascorbic acid biosynthesis, was used to investigate the effects of ascorbic acid deficiency on the hepatic gene expression of both the positive acute phase proteins, haptoglobin and alpha1-acid glycoprotein, and the negative acute phase proteins, apolipoprotein A-I and albumin. Male ODS rats (6 wk old, body weight approximately 140 g) were fed a basal diet containing ascorbic acid (300 mg/kg diet) or a diet without ascorbic acid for 14 d. Ascorbic acid deficiency significantly elevated the serum concentration of haptoglobin and significantly lowered those of apolipoprotein A-I and albumin. The hepatic mRNA levels of haptoglobin and alpha1-acid glycoprotein in the ascorbic acid-deficient rats were significantly elevated on d 12, and reached 260 (P < 0.05) and 360% (P < 0.01) of respective values in the control rats on d 14. On the contrary, the hepatic mRNA levels of apolipoprotein A-I and albumin in the ascorbic acid-deficient rats were lowered to 68 (P < 0.01) and 71% (P < 0.05) of respective values in the control rats on d 14. Although ascorbic acid deficiency significantly elevated the serum corticosterone concentration on d 14, the changes in mRNA levels of haptoglobin, alpha1-acid glycoprotein, apolipoprotein A-I and albumin due to ascorbic acid deficiency were not affected by adrenalectomy, as assessed in a separate experiment. The serum concentration of interleukin-6, an inflammatory cytokine that stimulates gene expression of some acute phase proteins, was significantly higher in the ascorbic acid-deficient rats on d 14 than in the control rats. These results suggest that ascorbic acid deficiency causes physiologic changes similar to those that occur in the acute phase response.
抗坏血酸生物合成存在遗传性缺陷的ODS大鼠（基因型od/od）被用于研究抗坏血酸缺乏对肝脏中正向急性期蛋白（触珠蛋白和α1-酸性糖蛋白）以及负向急性期蛋白（载脂蛋白A-I和白蛋白）基因表达的影响。雄性ODS大鼠（6周龄，体重约140克）被喂食含抗坏血酸（300毫克/千克饲料）的基础饲料或不含抗坏血酸的饲料14天。抗坏血酸缺乏显著提高了触珠蛋白的血清浓度，并显著降低了载脂蛋白A-I和白蛋白的血清浓度。在第12天，抗坏血酸缺乏大鼠肝脏中触珠蛋白和α1-酸性糖蛋白的mRNA水平显著升高，到第14天分别达到对照大鼠相应值的260%（P<0.05）和360%（P<0.01）。相反，在第14天，抗坏血酸缺乏大鼠肝脏中载脂蛋白A-I和白蛋白的mRNA水平降至对照大鼠相应值的68%（P<0.01）和71%（P<0.05）。尽管抗坏血酸缺乏在第14天显著提高了血清皮质酮浓度，但在另一项实验中评估发现，抗坏血酸缺乏导致的触珠蛋白、α1-酸性糖蛋白、载脂蛋白A-I和白蛋白mRNA水平的变化不受肾上腺切除术的影响。炎症细胞因子白细胞介素-6可刺激一些急性期蛋白的基因表达，在第14天，抗坏血酸缺乏大鼠血清中白细胞介素-6的浓度显著高于对照大鼠。这些结果表明，抗坏血酸缺乏会引起类似于急性期反应中出现的生理变化。
