de Bragança Ana C, Volpini Rildo A, Mehrotra Purvi, Andrade Lúcia, Basile David P
Division of Nephrology, Laboratory of Basic Science LIM-12, University of São Paulo School of Medicine, São Paulo, Brazil
Division of Nephrology, Laboratory of Basic Science LIM-12, University of São Paulo School of Medicine, São Paulo, Brazil.
Physiol Rep. 2016 Jul;4(13). doi: 10.14814/phy2.12829.
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.
肾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（AKI）后慢性肾脏病（CKD）的进展中起关键作用。维生素D缺乏与IRI-AKI后的肾小管间质损伤和纤维化进展相关。我们评估了维生素D缺乏在持续性IRI-AKI中的作用，推测这种缺乏会导致肾毛细血管密度早期降低或改变淋巴细胞对IRI的反应。将Wistar大鼠喂食无维生素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缺乏组（VDD）、双侧IRI组和VDD+IRI组。在手术操作后长达7天评估肾损伤和恢复指标。即使在没有肾I/R的情况下，VDD大鼠的毛细血管密度也降低（通过苏木精染色）。与VDD和IRI大鼠相比，VDD+IRI大鼠表现出毛细血管稀疏明显加重，以及更高的尿量、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。VDD+IRI大鼠还具有更多浸润的活化CD4(+)和CD8(+)细胞，这些细胞对干扰素γ和白细胞介素-17染色，Th17/调节性T细胞比值显著升高。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AKI转变为CKD。
