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尿毒症大鼠肠道铝吸收及分布的超灵敏分析:一项采用加速器质谱法的26Al示踪研究

Ultrasensitive analysis of the intestinal absorption and compartmentalization of aluminium in uraemic rats: a 26Al tracer study employing accelerator mass spectrometry.

作者信息

Ittel T H, Steinhausen C, Kislinger G, Kinzel S, Nolte E, Sieberth H G

机构信息

Department of Internal Medicine II, RWTH, Aachen, Germany.

出版信息

Nephrol Dial Transplant. 1997 Jul;12(7):1369-75. doi: 10.1093/ndt/12.7.1369.

Abstract

BACKGROUND

Developments in accelerator mass spectrometry (AMS) now permit the determination of femtogram amounts of 26Al in blood and in various tissues with good precision and free of external contamination.

METHODS

In the present study we used trace quantities of 26Al to investigate the intestinal absorption and compartmentalization of aluminium in rats with renal failure (Nx, 5/6 nephrectomy) and in pair-fed controls (C). Single oral doses of 20 ng 26Al were administered to six animals in each group and, subsequently, 24-h post-load 26Al was analysed in serum, urine, bone, liver, and spleen by means of AMS.

RESULTS

Serum concentrations of 26Al were significantly lower in uraemic rats compared to controls, whereas urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs C, 9.46 +/- 6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum 26Al in uraemia. The target tissues of cellular transferrin-mediated 26Al uptake, liver and spleen, tended to show a larger degree of aluminium accumulation in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27 pg/g vs Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site of extracellular aluminium deposition, 26Al concentrations were more elevated in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g). Estimated total 26Al accumulation in all measured target tissues was significantly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/- 7.03 pg) and total recovery of 26Al from tissue and urine was 26.58 +/- 6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a fractional absorption of 0.133% and 0.175% respectively.

CONCLUSIONS

Our data suggest that fractional absorption from a dietary level dose of 26Al is about 0.13%. Compartmentalization occurs in transferrin-dependent target tissues such as liver and spleen; however, in quantitative terms extracellular deposition in bone is more important. Uraemia has a significant effect on the intestinal absorption and compartmentalization of aluminium. It enhances fractional absorption and increases subsequent extracellular deposition of aluminium in bone. However, at the same time uraemia does not increase transferrin-dependent cellular accumulation of aluminium in liver and spleen.

摘要

背景

加速器质谱(AMS)技术的发展使得精确测定血液和各种组织中飞克量的26Al成为可能,且不受外部污染。

方法

在本研究中,我们使用痕量的26Al来研究肾衰竭大鼠(Nx,5/6肾切除)和配对喂养对照组(C)中铝的肠道吸收和分布情况。每组给6只动物单次口服20 ng 26Al,随后通过AMS分析负荷后24小时血清、尿液、骨骼、肝脏和脾脏中的26Al。

结果

与对照组相比,尿毒症大鼠血清中26Al浓度显著降低,而尿排泄量相当(Nx组为7.11±5.78 pg/天,C组为9.46±6.10 pg/天),这表明尿毒症时血清中可超滤的26Al比例更高。细胞转铁蛋白介导的26Al摄取的靶组织肝脏和脾脏,在对照组中铝的蓄积程度往往更大(分别为0.26±0.31 pg/g对Nx组的0.14±0.10 pg/g和0.37±0.27 pg/g对Nx组的0.25±0.27 pg/g)。相反,在细胞外铝沉积部位骨骼中,尿毒症时26Al浓度更高(1.22±0.59 pg/g对C组的0.68±0.30 pg/g)。尿毒症大鼠所有测量靶组织中26Al的估计总蓄积量显著高于对照组(28.15±9.90 pg对C组的17.03±7.03 pg),对照组从组织和尿液中回收的26Al总量为26.58±6.74 pg,尿毒症动物为35.75±7.03 pg,提示分别有0.133%和0.175%的吸收分数。

结论

我们的数据表明,饮食水平剂量的26Al的吸收分数约为0.13%。在转铁蛋白依赖性靶组织如肝脏和脾脏中发生分布;然而,从数量上看,骨骼中的细胞外沉积更为重要。尿毒症对铝的肠道吸收和分布有显著影响。它增加吸收分数并增加随后铝在骨骼中的细胞外沉积。然而,与此同时,尿毒症并不会增加转铁蛋白依赖性铝在肝脏和脾脏中的细胞蓄积。

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