Medical Research Unit in Nephrological Diseases, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Immunnology and Proteomics Research Lab, Hospital Infantil de México Federico Gómez, Mexico City, Mexico.
Arch Med Res. 2024 Apr;55(3):102969. doi: 10.1016/j.arcmed.2024.102969. Epub 2024 Mar 13.
Uremic toxicity changes the gut structure and permeability, allowing bacterial toxins to translocate from the lumen to the blood during chronic kidney failure (CKD). Clinical fluid overload and tissue edema without uremia have similar effects but have not been adequately demonstrated and analyzed in CKD.
To investigate the effect of sodium intake on the plasma concentration of gut-derived uremic toxins, indoxyl sulfate (IS), and p-cresyl sulfate (pCS) and the expression of genes and proteins of epithelial gut tight junctions in a rat model of CKD.
Sham-operated (control group, CG) and five-sixths nephrectomized (5/6Nx) Sprague-Dawley rats were randomly assigned to low (LNa), normal (NNa), or high sodium (HNa) diets., Animals were then sacrificed at 8 and 12 weeks and analyzed for IS and pCS plasma concentrations, as well as for gene and protein expression of thigh junction proteins, and transmission electron microscopy (TEM) in colon fragments.
The HNa 5/6Nx groups had higher concentrations of IS and pCS than CG, NNa, and LNa at eight and twelve weeks. Furthermore, HNa 5/6Nx groups had reduced expression of the claudin-4 gene and protein than CG, NNa, and LNa. HNa had reduced occludin gene expression compared to CG. Occludin protein expression was more reduced in HNa than in CG, NNa, and LNa. The gut epithelial tight junctions appear dilated in HNa compared to NNa and LNa in TEM.
Dietary sodium intake and fluid overload have a significant role in gut epithelial permeability in the CKD model.
尿毒症毒素会改变肠道结构和通透性，使细菌毒素在慢性肾衰竭（CKD）期间从肠腔转移到血液中。临床液体超负荷和无尿毒症的组织水肿具有相似的作用，但在 CKD 中尚未得到充分证明和分析。
研究钠摄入量对肠道来源尿毒症毒素吲哚硫酸（IS）和对甲酚硫酸（pCS）的血浆浓度以及 CKD 大鼠模型中肠上皮紧密连接的基因和蛋白表达的影响。
假手术（对照组，CG）和六分之五肾切除术（5/6Nx）Sprague-Dawley 大鼠被随机分配到低（LNa）、正常（NNa）或高钠（HNa）饮食组。然后在 8 和 12 周时处死动物，并分析 IS 和 pCS 的血浆浓度，以及股间连接蛋白的基因和蛋白表达，以及结肠片段的透射电镜（TEM）。
HNa 5/6Nx 组在 8 周和 12 周时的 IS 和 pCS 浓度均高于 CG、NNa 和 LNa。此外，HNa 5/6Nx 组的 claudin-4 基因和蛋白表达低于 CG、NNa 和 LNa。与 CG 相比，HNa 的 occludin 基因表达减少。与 CG、NNa 和 LNa 相比，HNa 的 occludin 蛋白表达减少更多。TEM 显示，与 NNa 和 LNa 相比，HNa 组的肠上皮紧密连接似乎扩张。
饮食钠摄入量和液体超负荷在 CKD 模型中对肠道上皮通透性有重要作用。
