Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury.
Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury.
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DOI：
10.14814/phy2.12829
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发表时间：
2016-07
影响因子：
2.5
通讯作者：
Basile DP
中科院分区：
文献类型：
--
作者：
de Bragança AC;Volpini RA;Mehrotra P;Andrade L;Basile DP
肾脏微血管密度降低和淋巴细胞活性增加可能在缺血/再灌注损伤（IRI）诱导的急性肾损伤（阿基）后慢性肾脏疾病（CKD）的进展中起关键作用。维生素D缺乏与阿基后肾小管间质损伤和纤维化进展相关。我们评估了维生素D缺乏对持续性阿基的影响，假设这种缺乏有助于早期肾毛细血管密度降低或改变淋巴细胞对IRI的反应。Wistar大鼠喂食不含维生素D或标准饮食35天。在第28天，将大鼠随机分为四组：对照组、维生素D缺乏（VDD）组、双侧IRI组和VDD+IRI组。在手术后7天内评价肾损伤和恢复指数。VDD大鼠显示毛细血管密度降低（通过cablin染色），即使在没有肾I/R的情况下。与VDD和IRI大鼠相比，VDD+IRI大鼠表现出毛细血管稀疏显著加重以及尿量、肾重/体重比、组织损伤评分、成纤维细胞特异性蛋白-1和α-平滑肌肌动蛋白更高。VDD+IRI大鼠也有更多的浸润活化的CD 4+和CD 8+细胞染色的干扰素γ和白细胞介素-17，在Th 17/T调节细胞的比例显着升高。这些数据表明，维生素D缺乏会损害肾对I/R损伤的修复反应，加剧肾毛细血管密度的变化，以及促进纤维化和炎症，这可能有助于从阿基转变为CKD。
Reductions in renal microvasculature density and increased lymphocyte activity may play critical roles in the progression of chronic kidney disease (CKD) following acute kidney injury (AKI) induced by ischemia/reperfusion injury (IRI). Vitamin D deficiency is associated with tubulointerstitial damage and fibrosis progression following IRI‐AKI. We evaluated the effect of vitamin D deficiency in sustained IRI‐AKI, hypothesizing that such deficiency contributes to the early reduction in renal capillary density or alters the lymphocyte response to IRI. Wistar rats were fed vitamin D‐free or standard diets for 35 days. On day 28, rats were randomized into four groups: control, vitamin D deficient (VDD), bilateral IRI, and VDD+IRI. Indices of renal injury and recovery were evaluated for up to 7 days following the surgical procedures. VDD rats showed reduced capillary density (by cablin staining), even in the absence of renal I/R. In comparison with VDD and IRI rats, VDD+IRI rats manifested a significant exacerbation of capillary rarefaction as well as higher urinary volume, kidney weight/body weight ratio, tissue injury scores, fibroblast‐specific protein‐1, and alpha‐smooth muscle actin. VDD+IRI rats also had higher numbers of infiltrating activated CD4+ and CD8+ cells staining for interferon gamma and interleukin‐17, with a significant elevation in the Th17/T‐regulatory cell ratio. These data suggest that vitamin D deficiency impairs renal repair responses to I/R injury, exacerbates changes in renal capillary density, as well as promoting fibrosis and inflammation, which may contribute to the transition from AKI to CKD.