Liang Hu, Xu Yuexian, Sun Shuai, Chen Yang, Wang Wei, Hao Zongyao
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Institute of Urology, Anhui Medical University, Hefei, China.
Urolithiasis. 2024 Dec 12;53(1):3. doi: 10.1007/s00240-024-01673-1.
The commencement of kidney stone formation involves a crucial initial phase characterized by injury to renal tubular cells caused by calcium oxalate (CaOx). Dioscin (Dio) has been acknowledged for its potent anti-inflammation and anti-apoptotic properties; nevertheless, the impact and underlying Investigation into the molecular basis underlying the action of Dioscin in mitigating inflammation and apoptotic induced by exposure to calcium oxalate crystals in renal tissues remain unexplored. To comprehend the precise mechanism of Dioscin in the treatment of crystalline nephropathy, we conducted experiments utilizing a murine model of CaOx crystal deposition, induced by intraperitoneal administration of glyoxylate. An in vitro model was constructed using HK-2 cells exposed to calcium oxalate monohydrate (COM). To evaluate the effect of Dioscin on calcium oxalate crystal deposition by ROS assay, Western blotting, immunohistochemistry, Periodic Acid-Schiff staining (PAS) staining, hematoxylin-eosin (H&E) staining. Using network pharmacology and molecular docking methods, we explored the molecular mechanism of Dioscin in the treatment of CaOx-induced renal tubular epithelial cell injury. Subsequently, we conducted experiments to verify our findings. We observed a significant protective effect of Dioscin treatment against kidney oxidative stress and inflammation induced by CaOx. Then we predicted through network pharmacology that Dioscin exerts its anti-apoptotic effect through the NF-kappa B signaling pathway. Then we verified in vitro and in vivo that administration of Dioscin can alleviate the elevation of TLR4 and activation of the NF-kappa B signaling pathway induced by calcium oxalate, as well as attenuate renal apoptosis. Instead, the beneficial impact of this protection of Dioscin was reversed after overexpression of the TLR4. Dioscin has the potential to alleviate the activation of the NF-kappa B signaling pathway through TLR4, thereby exerting anti-inflammatory and anti-apoptotic effects. This study provides new ideas for the prevention and treatment of kidney stones.
肾结石形成的起始涉及一个关键的初始阶段，其特征是草酸钙（CaOx）对肾小管细胞造成损伤。薯蓣皂苷（Dio）因其强大的抗炎和抗凋亡特性而得到认可；然而，薯蓣皂苷在减轻肾组织中暴露于草酸钙晶体所诱导的炎症和凋亡方面的作用及其潜在的分子基础仍未得到探索。为了理解薯蓣皂苷治疗结晶性肾病的精确机制，我们利用腹腔注射乙醛酸诱导的CaOx晶体沉积小鼠模型进行了实验。使用暴露于一水合草酸钙（COM）的HK - 2细胞构建了体外模型。通过活性氧测定、蛋白质印迹、免疫组织化学、过碘酸 - 希夫染色（PAS）、苏木精 - 伊红染色（H&E）来评估薯蓣皂苷对草酸钙晶体沉积的影响。我们使用网络药理学和分子对接方法，探索了薯蓣皂苷治疗CaOx诱导的肾小管上皮细胞损伤的分子机制。随后，我们进行实验以验证我们的发现。我们观察到薯蓣皂苷治疗对CaOx诱导的肾脏氧化应激和炎症具有显著的保护作用。然后我们通过网络药理学预测薯蓣皂苷通过NF - κB信号通路发挥其抗凋亡作用。然后我们在体外和体内验证了给予薯蓣皂苷可以减轻草酸钙诱导的TLR4升高和NF - κB信号通路的激活，以及减轻肾脏凋亡。相反，在TLR4过表达后，薯蓣皂苷这种保护的有益影响被逆转。薯蓣皂苷有可能通过TLR4减轻NF - κB信号通路的激活，从而发挥抗炎和抗凋亡作用。本研究为肾结石的预防和治疗提供了新的思路。
