Department of Pediatric Surgery, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, 730050, Gansu, China.
Department of Pediatric General Medicine, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, 730050, Gansu, China.
J Nanosci Nanotechnol. 2021 Feb 1;21(2):1266-1271. doi: 10.1166/jnn.2021.18655.
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 , 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.
金纳米颗粒（GNPs）由于其制备简单、物理化学性质稳定、光学性质可控且毒性较小，因此在生命科学和医学中得到了广泛的应用。然而，近年来的研究发现，金纳米颗粒在生物医学领域的应用仍存在许多不确定因素，而且关于其主要排泄器官和肾脏的研究较少，尤其是在疾病状态下的毒理学效应尚未报道。显然，开展相关研究对于加速金纳米颗粒的临床应用具有重要意义。慢性肾脏病（CKD）是一组慢性进行性疾病，其患病率和死亡率均较高，严重威胁着人类的生命和健康。肾小管损伤和间质纤维化是慢性肾脏病肾功能障碍的关键因素。药物和毒性肾损伤主要涉及肾小管上皮细胞；缺氧是细胞最常见的病理状态。在肾脏病变中，肾小管上皮细胞常发生缺氧。基于此，我们提出了本研究的假设：肾脏疾病时肾小球滤过膜损伤，GNPs 增加进入尿液，随后被肾小管上皮细胞重吸收，从而对后者造成损伤；如果伴有缺氧，GNPs 会加重肾小管上皮细胞损伤，促进肾小管间质纤维化。为了验证上述假设，本研究采用阿霉素肾病小鼠模型和肾小管上皮细胞及巨噬细胞，通过多种手段观察 GNPs 对肾小管上皮细胞的损伤，并探讨相关机制。结果表明，在正常氧条件下，GNPs 进入细胞后可诱导自噬，自噬可损伤受损的蛋白质和细胞器，从而维持细胞存活。在缺氧条件下，纳米颗粒进入细胞的数量增加，并诱导过度自噬。在缺氧条件下，GNPs 也会在巨噬细胞中聚集，这会导致细胞增殖活性降低，并诱导巨噬细胞炎症小体的激活，从而引发炎症反应：可以促进 GNPs 诱导的缺氧巨噬细胞的分泌。
