Mechanism of autophagy on the formation of kidney stones caused by calcified nanoparticles / 医学研究生学报

ABSTRACT

Objective　The relationship between calcified nanoparticles (CNPs) and the formation of urinary stones is drawing increasing attention and the specific mechanisms involved. This study aims to investigate the mechanisms of the formation of kidney stone caused by CNPs.　Methods　A total of 48 rats were randomly and equally divided into a CNPs group (each rat was injected with 2 mL CNPs through the tail vein to establish a rat kidney stone model of CNPs), and a control group (injected the same amount of sterile isotonic saline instead of CNPs). We compared the expression levels of autophagy-related proteins, such as Beclin-1 and LC-3, the formation of autophagosomes and calcium salt crystals in renal tissues at time points of 3h, 6h, 12h, 24h, 1w, 2w, 4w and 8w in two groups.　Results　The relative expression levels and positive cells of Beclin-1 and LC-3 in CNPs group at 3h,6h,12h,24h, 1w, 2w, 4w, 8w were significantly higher than those in the control group (P< 0.05), and reached the highest value at 24 (P< 0.05). The number of autophagosomes at 24h, 1w, 2w, 4w, and 8w in the CNPs group ((2.83±0.32), (3.00±0.26), (3.70±0.44), (3.90±0.98), (4.70±0.51)/HP, respectively) were significantly higher than those in the control group (0.73±0.15)/HP (P <0.05). The scores of calcium salt crystals in the CNPs group at 2w, 4w, and 8w significantly increased compared to the control group (P <0.05). The calcium salt crystal formation score ((0.92 ± 0.98) points) was positively correlated with the expression intensities of Beclin-1 and LC-3 ((6.78 ± 4.25), (2.61 ± 2.57), respectively) (r = 0.843, 0.628, P <0.05), which was positively correlated with the number of autophagosomes (2.53 ± 1.41) (r = 0.923, P <0.001).　Conclusion　CNPs may damage renal tubular epithelial cells, and induce immediate autophagic activity, also increase expression of autophagy-related proteins and autophagosome formation, which will promote the formation and aggregation of calcium salt crystals in renal tubules to some extent.