Age-related alteration of vitamin D metabolism in response to low-phosphate diet in rats
Age-related alteration of vitamin D metabolism in response to low-phosphate diet in rats
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DOI：
10.1079/bjn20041325
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发表时间：
2005-03-01
影响因子：
3.6
通讯作者：
Wong, MS
中科院分区：
文献类型：
--
作者：
Chau, TS;Lai, WP;Wong, MS
肾脏维生素D代谢对其主要刺激的反应随年龄而改变。先前的研究表明，随着大鼠年龄的增长，对饮食钙或磷限制的反应，循环1，25-二羟基维生素D（1，25（OH）（2）D-3）以及肾脏25-羟基维生素D-3 1-α羟化酶（1-OHase）活性的增加减少。我们假设，增加循环1，25（OH）2D 3的机制，以响应矿物质缺乏改变与年龄有关。在本研究中，我们通过研究参与肾脏维生素D代谢的基因（肾脏1-OHase，25-羟基维生素D 24-羟化酶（24-OHase）和维生素D受体（VDR））在年轻（1个月大）和成年（6个月大）大鼠低磷饮食（LPD）的表达来验证这一假设。正如预期，LPD给药后，幼龄和成年大鼠的血清1，25（OH）（2）D-3均升高，且幼龄大鼠的升高幅度更高。在幼年大鼠中，LPD治疗降低肾脏24-OHase（1-7天，P < 0.01），增加肾脏1-OHase mRNA表达（1-5天，P < 0.01）。LPD处理7 d内未引起肾组织1-OHase的升高，但抑制了24-OHase mRNA的表达（P < 0.01）。肾脏VDR mRNA表达随年龄增长而降低（P < 0.001），LPD治疗后两个年龄组肾脏VDR mRNA表达均受到抑制（P < 0.05）。成年大鼠灌胃LPD 10 d后，1-OHase表达增加（P < 0.05），24-OHase表达下降（P < 0.001），VDR mRNA表达下降（P < 0.05）。这些结果表明，短期LPD治疗期间成年大鼠血清1，25（OH）2D 3水平的升高可能是通过下调肾脏24-OHase和VDR表达而导致代谢清除率降低介导的。成年大鼠肾脏1-OHase mRNA表达的诱导需要比年轻大鼠更长的LPD治疗持续时间。
The responses of renal vitamin D metabolism to its major stimuli alter with age. Previous studies showed that the increase in circulating 1,25-dihydroxyvitamin D (1,25(OH)(2)D-3) as well as renal 25-hydroxyvitamin D-3 1-alpha hydroxylase (1-OHase) activity in response to dietary Ca or P restriction reduced with age in rats. We hypothesized that the mechanism involved in increasing circulating 1,25( OH) 2D3 in response to mineral deficiency alters with age. In the present study, we tested the hypothesis by studying the expression of genes involved in renal vitamin D metabolism (renal 1-OHase, 25-hydroxyvitamin D 24-hydroxylase (24-OHase) and vitamin D receptor (VDR)) in young (1-month-old) and adult (6-month-old) rats in response to low-phosphate diet (LPD). As expected, serum 1,25(OH)(2)D-3 increased in both young and adult rats upon LPD treatment and the increase was much higher in younger rats. In young rats, LPD treatment decreased renal 24-OHase (days 1-7, P < 0.01) and increased renal 1-OHase mRNA expression (days 1-5, P < 0.01). LPD treatment failed to increase renal 1-OHase but did suppress 24-OHase mRNA expression (P < 0.01) within 7 d of LPD treatment in adult rats. Renal expression of VDR mRNA decreased with age (P < 0.001) and was suppressed by LPD treatment in both age groups ( P < 0.05). Feeding of adult rats with 10 d of LPD increased 1-OHase (P < 0.05) and suppressed 24-OHase ( P < 0.001) as well as VDR (P < 0.05) mRNA expression. These results indicate that the increase in serum 1,25(OH) 2D3 level in adult rats during short-term LPD treatment is likely to be mediated by a decrease in metabolic clearance via the down-regulation of both renal 24-OHase and VDR expression. The induction of renal 1-OHase mRNA expression in adult rats requires longer duration of LPD treatment than in younger rats.