Albuminuria is a primary feature in patients with CKD and an important contributor to tubulointerstitial fibrosis (TIF) development. Autophagy has been considered to be involved in renal tubular injury caused by albuminuria. Fe₃O₄ magnetic nanoparticles are related to many cellular activities, such as autophagy and inflammation. Rab7, a molecule involved in both endocytosis and autophagy, has been identified to protect renal tubular epithelial cells from albumin by regulating autophagy and MMP-2 activity in the early stage of albumin stimulation, but its role in the advanced stage is still unclear. Therefore, to investigate the effect of Fe₃O₄ magnetic nanoparticles on chronic renal tubular injury induced by excess albumin and to further determine the specific role of Rab7, we established a mouse model of TIF by intravenous injection of cationic bovine serum albumin (C-BSA) in Rab7-overexpressing transgenic mice. Our data revealed the decreased autophagy level, weakened MMP-2 activity and exacerbated renal tubular injury in these BSA-overloaded mice; furthermore, the degree of injury was more serious in Rab7-overexpressing transgenic mice. However, the application of Fe₃O₄ magnetic albumin nanoparticles (Fe₃O₄@BSA) enhanced MMP-2 activity and alleviated renal tubular injury, and these changes were mediated by an autophagy-dependent mechanism. Taken together, our results indicated that long-term albumin stimulation combined with overexpression of Rab7 could further decrease MMP-2 activity, exacerbate renal tubular injury and accelerate the development of TIF. Fe₃O₄@BSA could be a promising targeted tool for the management of CKD patients.

蛋白尿是CKD患者的主要特征，也是肾小管间质纤维化（TIF）发展的重要因素。自噬被认为与白蛋白尿引起的肾小管损伤有关。Fe ₃ O ₄磁性纳米颗粒与许多细胞活动有关，例如自噬和炎症。Rab7是一种参与内吞和自噬的分子，已被确定可通过在白蛋白刺激的早期阶段调节自噬和MMP-2活性来保护肾小管上皮细胞免受白蛋白的侵害，但其在晚期的作用尚不清楚。因此，要研究Fe ₃ O _4的作用磁性纳米颗粒对过量白蛋白引起的慢性肾小管损伤的影响，并进一步确定Rab7的特定作用，我们通过在过表达Rab7的转基因小鼠中静脉注射阳离子牛血清白蛋白（C-BSA）建立了TIF小鼠模型。我们的数据显示，这些BSA超负荷小鼠的自噬水平降低，MMP-2活性减弱并加重了肾小管损伤。此外，在过度表达Rab7的转基因小鼠中损伤程度更为严重。然而，Fe ₃ O ₄磁性白蛋白纳米颗粒（Fe ₃ O ₄@BSA）可增强MMP-2活性并减轻肾小管损伤，这些变化是由自噬依赖性机制介导的。两者合计，我们的结果表明，长期的白蛋白刺激与Rab7的过度表达可能进一步降低MMP-2活性，加剧肾小管损伤并加速TIF的发展。Fe ₃ O ₄ @BSA可能是有前景的针对CKD患者的靶向治疗工具。