肾结石是常见疾病，严重影响患者的健康和生活质量。虽然报道了过山龙苷（Hyp）对肾结石的影响，但其具体机制尚未阐明。因此，本研究旨在探讨Hyp对肾损伤和草酸钙（CaOx）晶体沉积的效应与潜在机制。采用乙二醇（EG）和CaOx诱导构建大鼠和细胞肾结石模型。使用HE染色、Pizzolato染色和血液和尿液参数的生化检测评估大鼠的肾组织病理损伤、CaOx晶体沉积和肾功能损伤。利用MTT和晶体-细胞粘附实验确定HK-2细胞的活性和晶体粘附能力，使用生化检测和酶联免疫吸附法（ELISA）检测氧化应激相关物质和炎症因子的水平，以及使用西方印迹检测与AMPK / Nrf2信号通路相关的蛋白表达水平。总之，Hyp可以改善大鼠肾组织病理损害和肾功能障碍，减少肾结石大鼠肾组织中的CaOx晶体沉积，减少晶体对CaOx处理的HK-2细胞的粘附。此外，Hyp还显著抑制了氧化应激反应。此外，Hyp与丙二醛、乳酸脱氢酶和活性氧的下调以及超氧化物歧化酶活性的上调相关。此外，Hyp治疗还抑制了炎症反应，与白细胞介素（IL）-1β、IL-6、IL-8和肿瘤坏死因子水平的下降相关。进一步探索表明，Hyp可能通过促进AMPK磷酸化和Nrf2的核转运活化AMPK / Nrf2信号通路起到保护作用。 Hyp可以改善肾脏病理和功能损伤，降低CaOx晶体沉积，抑制氧化应激和炎症反应。这些效应可能通过激活AMPK / Nrf2信号通路实现。版权所有©2023年Hongyang Tian等。

Nephrolithiasis is a common disease that seriously affects the health and life quality of patients. Despite the reported effect of hyperoside (Hyp) against nephrolithiasis, the specific mechanism has not been clarified. Therefore, this study is aimed at investigating the effect and potential mechanism of Hyp on renal injury and calcium oxalate (CaOx) crystal deposition.Rat and cell models of renal calculi were constructed by ethylene glycol (EG) and CaOx induction, respectively. The renal histopathological damage, CaOx crystal deposition, and renal function damage of rats were assessed by HE staining, Pizzolato staining, and biochemical detection of blood and urine parameters. MTT and crystal-cell adhesion assays were utilized to determine the activity of HK-2 cells and crystal adhesion ability, biochemical detection and enzyme-linked immunosorbent assay (ELISA) to measure the levels of oxidative stress-related substances and inflammatory factors, and western blot to test the expression levels of proteins related to the AMPK/Nrf2 signaling pathway.Briefly speaking, Hyp could improve the renal histopathological injury and impaired renal function, reduce the deposition of CaOx crystals in the renal tissue of rats with renal calculi, and decrease the adhesion of crystals to CaOx-treated HK-2 cells. Besides, Hyp also significantly inhibited oxidative stress response. Furthermore, Hyp was associated with the downregulation of malondialdehyde, lactate dehydrogenase, and reactive oxygen species and upregulation of superoxide dismutase activity. Additionally, Hyp treatment also suppressed inflammatory response and had a correlation with declined levels of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor. Further exploration of mechanism manifested that Hyp might play a protective role through promoting AMPK phosphorylation and nuclear translation of Nrf2 to activate the AMPK/Nrf2 signaling pathway.Hyp can improve renal pathological and functional damage, decrease CaOx crystal deposition, and inhibit oxidative stress and inflammatory response. Such effects may be achieved by activating the AMPK/Nrf2 signaling pathway.Copyright © 2023 Hongyang Tian et al.