Nicotinamide prevents the development of hyperphosphataemia by suppressing intestinal sodium-dependent phosphate transporter in rats with adenine-induced renal failure
Nicotinamide prevents the development of hyperphosphataemia by suppressing intestinal sodium-dependent phosphate transporter in rats with adenine-induced renal failure
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DOI：
10.1093/ndt/gfh781
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发表时间：
2005-07-01
影响因子：
6.1
通讯作者：
Yamashita, T
中科院分区：
文献类型：
--
作者：
Eto, N;Miyata, Y;Yamashita, T
背景资料。烟酰胺被证明能抑制正常大鼠肠道钠依赖的磷酸盐转运活动。新近报道，IIb型钠依赖磷酸共转运体(Napi-2b)是肠道磷酸盐吸收的载体，其表达水平受正常大鼠血清1，25-二羟基维生素D[1，25(OH)D-2]和PI水平的调节。然而，在慢性肾功能衰竭(CRF)中，血清1，25(OH)D-2和PI水平往往异常。在慢性肾功能衰竭大鼠模型上，我们研究了短期给予烟酰胺是否有效地减少了肠道磷酸盐的吸收，如果是的话，这种作用是否由肠道Napi-2b介导。以腺嘌呤诱导的CRF大鼠为模型，每日单次内注射烟酰胺或溶媒溶液，连续6d，监测血清PI、Ca、尿素氮(BUN)和肌酐水平的时程变化。最后一天口服放射性标记磷酸盐检查肠道磷酸盐吸收。此外，还测定了空肠刷状缘膜中NAPI-2b蛋白含量。烟酰胺可阻止与肾功能衰竭相关的血清PI进行性升高，并显著抑制肠道PI的吸收，通过口服放射性标记磷酸盐进入循环进行评估。伴随这一效应的是空肠刷状缘膜中napi-2b的表达减少。此外，烟酰胺治疗后血尿素氮和血肌酐升高较少，而内生肌酐清晰度较高。烟酰胺抑制CRF模型大鼠的肠道PI吸收，至少部分是通过抑制Napi-2b的表达，并似乎对肾功能恶化具有保护作用。
Background. Nicotinamide has been shown to inhibit intestinal sodium-dependent phosphate transport activity in normal rats. It was reported recently that type IIb sodium-dependent phosphate co-transporter (NaPi-2b) is a carrier of intestinal phosphate absorption, and that its expression level is regulated by serum 1,25-dihydroxyvitamin D [1,25(OH)D-2] and Pi levels in normal rats. However, in chronic renal failure (CRF), serum 1,25(OH)D-2 and Pi levels are often abnormal. In a rat model of CRF, we investigated whether short-term nicotinamide administration was effective in reducing intestinal phosphate absorption and, if so, whether the effect was mediated by intestinal NaPi-2b.Methods. Adenine-induced CRF rats were given a single daily intrapenitoneal administration of nicotinamide or vehicle solution for 6 days, and time course changes in serum Pi, Ca, blood urea nitrogen (BUN) and creatinine levels were monitored. Intestinal phosphate absorption was examined by oral administration of radiolabelled phosphate on the final day. In addition, NaPi-2b protein content in jejunum brush border membranes was determined.Results. Nicotinamide prevented the progressive increase in serum Pi associated with renal failure and significantly inhibited intestinal Pi absorption as assessed by the influx of orally administered radiolabelled phosphate into the circulation. This effect was accompanied by a decrease in NaPi-2b expression in jejunum brush border membranes. In addition, nicotinamide treatment was also associated with less marked elevations in BUN and serum creatinine and a higher creatinine clearance.Conclusions. Nicotinamide inhibited intestinal Pi absorption in a rat model of CRF, at least in part by inhibiting the expression of NaPi-2b, and appeared to protect against the deterioration of renal function.