Gold nanoparticles (GNPs) are widely used in life sciences and medicine due to their simple preparation, stable physical and chemical properties, controllable optical properties and no significant toxicity. However, in recent years, studies have found that there are still many uncertain factors in the application of
gold nanoparticles in the field of biomedicine, and there are few studies on the main excretion organs and kidneys of the body, especially the toxicological effects under the disease state have not been reported. Obviously, carrying out relevant research is of great significance for accelerating the clinical application of GNPs.
Chronic kidney disease (CKD) is a group of chronic progressive diseases that have high prevalence and high mortality and are serious threats to human life and health. Renal tubular injury and interstitial
fibrosis are key factors in renal dysfunction in
chronic kidney disease. Drug and toxic kidney damage mostly involve renal tubular epithelial cells;
hypoxia is the most common pathological condition of cells. In renal lesions, renal tubular epithelial cells often have
hypoxia. Based on this, we propose the hypothesis of this study: glomerular filtration membrane damage in
kidney disease, GNPs increase in urine, followed by reabsorption of renal tubular epithelial cells, thereby causing damage to the latter; if accompanied by
hypoxia, GNPs it will aggravate renal tubular epithelial cell damage and promote tubulointerstitial
fibrosis. In order to verify the above hypothesis, this study used a mouse model of
adriamycin nephropathy and tubular epithelial cells and macrophages in vitro, and observed the damage of GNPs on renal tubular epithelial cells by various means, and explored related mechanisms. The results show that under normal
oxygen conditions, GNPs can induce autophagy after cell entry, which can damage damaged
proteins and organelles to maintain cell survival. In the absence of
oxygen, nanoparticles entering cells increase and induce excessive autophagy. In the absence of
oxygen, GNPs also aggregate in macrophages, which can cause decreased cell proliferation activity and induce activation of macrophage
inflammasome, which induces inflammatory response: GNPs-induced secretion of hypoxic macrophages can be promoted.