Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
Department of prevention and treatment of contagious diseases, HeZe City Center for disease control and prevention, HeZe, Shandong 274000, PR China.
Phytomedicine. 2019 Aug;61:152861. doi: 10.1016/j.phymed.2019.152861. Epub 2019 Feb 4.
Nephrolithiasis is one of the most common and frequent urologic diseases worldwide. Several pathophysiological mechanisms are involved in stone formation, including oxidative stress, inflammation, apoptosis, fibrosis and autophagy. Curcumin, the predominant active component of turmeric, has been shown to have pleiotropic biological and pharmacological properties, such as antioxidant, anti-inflammatory and antifibrotic effects.
The current study proposed to systematically investigate the protective effects and the underlying mechanisms of curcumin in a calcium oxalate (CaOx) nephrolithiasis mouse model.
The animal model was established in male C57BL/6 mice by successive intraperitoneal injection of glyoxylate (100 mg/kg) for 1 week. Curcumin was orally given to mice 7 days before the injection of glyoxylate and for a total of 14 days at 50 mg/kg or 100 mg/kg. Bilateral renal tissue was harvested and processed for oxidative stress index detection, histopathological examinations and other analyses.
Coadministration of curcumin could significantly reduce glyoxylate-induced CaOx deposition and simultaneous tissue injury in mouse kidneys. Meanwhile, curcumin alleviated the oxidative stress response via reducing MDA content and increasing SOD, CAT, GPx, GR and GSH levels in this animal model. Moreover, treatment with curcumin significantly inhibited apoptosis and autophagy induced by hyperoxaluria. Curcumin also attenuated the high expression of IL-6, MCP-1, OPN, CD44, α-SMA, Collagen I and collagen fibril deposition, which were elevated by hyperoxaluria. Furthermore, the results revealed that both the total expression and nuclear accumulation of Nrf2, as well as its main downstream products such as HO-1, NQO1 and UGT, were decreased in the kidneys of mice in the crystal group, while treatment with curcumin could rescue this deterioration.
Curcumin could significantly alleviate CaOx crystal deposition in the mouse kidney and the concurrent renal tissue injury. The underlying mechanism involved the combination of antioxidant, anti-apoptotic, inhibiting autophagy, anti-inflammatory, and antifibrotic activity and the ability to decrease expression of OPN and CD44 through the Nrf2 signaling pathway. The pleiotropic antilithic properties, combined with the minimal side effects, make curcumin a good potential choice to prevent and treat new or recurrent nephrolithiasis.
肾结石是全球最常见和最频繁的泌尿科疾病之一。结石形成涉及多种病理生理机制，包括氧化应激、炎症、细胞凋亡、纤维化和自噬。姜黄素是姜黄的主要活性成分，具有多种生物学和药理学特性，如抗氧化、抗炎和抗纤维化作用。
本研究旨在系统研究姜黄素在草酸钙（CaOx）肾结石小鼠模型中的保护作用及其潜在机制。
雄性 C57BL/6 小鼠通过连续腹腔注射乙醛酸（100mg/kg）1 周建立动物模型。在注射乙醛酸前 7 天开始给予姜黄素，连续 14 天，剂量为 50mg/kg 或 100mg/kg。采集双侧肾脏组织，进行氧化应激指标检测、组织病理学检查等分析。
姜黄素共给药可显著减少乙醛酸诱导的 CaOx 沉积和小鼠肾脏的同时组织损伤。同时，姜黄素通过降低 MDA 含量和增加 SOD、CAT、GPx、GR 和 GSH 水平，减轻该动物模型的氧化应激反应。此外，姜黄素治疗可显著抑制高草酸尿诱导的细胞凋亡和自噬。姜黄素还可抑制高草酸尿引起的 IL-6、MCP-1、OPN、CD44、α-SMA、I 型胶原和胶原纤维沉积的高表达。此外，结果表明，在晶体组小鼠肾脏中，Nrf2 的总表达和核积累以及其主要下游产物如 HO-1、NQO1 和 UGT 均降低，而姜黄素治疗可挽救这种恶化。
姜黄素可显著减轻小鼠肾脏中 CaOx 晶体沉积和肾脏组织损伤。其潜在机制涉及抗氧化、抗凋亡、抑制自噬、抗炎和抗纤维化活性的结合，以及通过 Nrf2 信号通路降低 OPN 和 CD44 表达的能力。姜黄素具有多种抗结石特性，且副作用极小，是预防和治疗新发性或复发性肾结石的良好选择。
