Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan.
Sci Rep. 2017 Sep 6;7(1):10621. doi: 10.1038/s41598-017-11089-0.
Increased proteinuria causes tubulointerstitial injury due to inflammation in chronic kidney disease (CKD). Iron restriction exhibits protective effects against renal dysfunction; however, its effects against protein overload-induced tubulointerstitial damage remain unclear. Here, we investigated dietary iron restriction effect on tubulointerstitial damage in mice with protein-overload tubulointerstitial injury. Renal tubulointerstitial injury in animal model was induced by intraperitoneal injection of an overdose of bovine serum albumin (BSA). We divided mice into three groups: normal saline + normal diet (ND), BSA + ND, and BSA + iron-restricted diet (IRD). BSA overload induced renal tubulointerstitial injury in the ND mice, which was ameliorated in the IRD mice. Inflammatory cytokines and extracellular matrix mRNA expression was upregulated in BSA + ND mice kidneys and was inhibited by IRD. BSA-induced increase in renal superoxide production, NADPH oxidase activity, and p22 expression was diminished in the IRD mice. IRD suppression increased BSA-induced renal macrophage infiltration. Moreover, BSA mice exhibited nucleotide-binding oligomerisation domain-like receptor pyrin domain-containing protein (NLRP) inflammasome activation, which was inhibited by IRD. Ferrous iron increased in kidneys with BSA overload and was inhibited by IRD. Thus, iron restriction inhibited oxidative stress and inflammatory changes, contributing to the protective effect against BSA overload-induced tubulointerstitial injury.
在慢性肾脏病（CKD）中，蛋白尿增加会导致炎症引起的肾小管间质损伤。铁限制对肾功能障碍具有保护作用；然而，其对蛋白过载诱导的肾小管间质损伤的作用仍不清楚。在这里，我们研究了饮食中铁限制对蛋白过载肾小管间质损伤小鼠肾小管间质损伤的影响。动物模型中的肾小管间质损伤通过腹腔注射过量牛血清白蛋白（BSA）来诱导。我们将小鼠分为三组：生理盐水+正常饮食（ND）、BSA+ND 和 BSA+铁限制饮食（IRD）。BSA 过载在 ND 小鼠中引起了肾小管间质损伤，而在 IRD 小鼠中则得到了改善。在 BSA+ND 小鼠的肾脏中，炎性细胞因子和细胞外基质 mRNA 的表达上调，并被 IRD 抑制。BSA 诱导的肾脏超氧化物产生、NADPH 氧化酶活性和 p22 表达增加在 IRD 小鼠中减少。IRD 抑制增加了 BSA 诱导的肾脏巨噬细胞浸润。此外，BSA 小鼠表现出核苷酸结合寡聚结构域样受体吡咯烷结构域包含蛋白（NLRP）炎性小体的激活，而 IRD 抑制了这一激活。铁过载时肾脏中的亚铁增加，IRD 抑制了这一增加。因此，铁限制抑制了氧化应激和炎症变化，有助于对抗 BSA 过载诱导的肾小管间质损伤。
