Identification of Resolvin D1 and Protectin D1 as Potential Therapeutic Agents for Treating Kidney Stones.
Identification of Resolvin D1 and Protectin D1 as Potential Therapeutic Agents for Treating Kidney Stones.
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DOI：
10.1155/2022/4345037
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发表时间：
2022
影响因子：
--
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Wang B;Wei J;Huangfu Q;Gao F;Qin L;Zhong J;Wen J;Ye Z;Yang X;Liu H
肾内草酸钙结晶可引起肾小管上皮细胞炎症和氧化损伤。这项研究的目的是探索肾结石中潜在的治疗脂质成分，因为脂质参与多种疾病的发展并表明肾结石的风险。收集35例肾结石患者和35例正常人的血清标本。测定血清脂质成分，并进行差异分析。对记录的生物学重要性进行了全面审查，以确定两组之间存在显著差异的脂质，从而发现与肾结石相关的潜在药物。建立CaOx肾钙质沉积小鼠模型，以检查特定脂质对CaOx沉积和CaOx诱导的氧化性肾损伤的治疗作用。结石患者和正常人血清中存在几种水平差异显著的脂质。肾结石患者血清中Resolvin D1（RvD1）（4.93倍变化，P < 0.001）和protectin D1（PD1）（5.06倍变化，P < 0.001）显著降低，综合综述表明这些因子可能与炎症反应相关，炎症反应是与结石损害相关的重要机制。在CaOx肾钙质沉着症小鼠模型中，给予RvD1和PD1显著抑制肾脏CaOx沉积并抑制CaOx诱导的肾小管细胞炎性损伤和坏死。此外，RvD1和PD1促进氧化指示剂超氧化物歧化酶2（SOD 2）的表达，抑制NADPH氧化酶2（NOX 2）的表达，并降低细胞内活性氧（ROS）水平。本研究初步阐明了脂质在肾结石中的作用。RvD1和PD1对CaOx沉积诱导的氧化损伤的抑制作用为肾结石治疗策略提供了有希望的前景。
Intrarenal calcium oxalate (CaOx) crystals induce renal tubular epithelial cell (TEC) inflammatory and oxidative injury. This study is aimed at exploring potential therapeutic lipid components in kidney stones because lipids are involved in the development of several diseases and indicate the risk of kidney stones. Serum specimens were collected from 35 kidney stone patients and 35 normal controls. The lipid components in serum were measured, and differences were analyzed. The documented biological importance was comprehensively reviewed to identify lipids that differed significantly between the two groups to find potential agents associated with kidney stones. CaOx nephrocalcinosis mouse model was established to examine the therapeutic effects of specific lipids on CaOx deposition and CaOx-induced oxidative renal injury. Several lipids with significantly different levels were present in the serum of patients with stones and normal controls. Resolvin D1 (RvD1) (4.93-fold change, P < 0.001) and protectin D1 (PD1) (5.06-fold change, P < 0.001) were significantly decreased in the serum of patients with kidney stones, and an integrative review suggested that these factors might be associated with inflammatory responses, which is a crucial mechanism associated with stone damage. The administration of RvD1 and PD1 significantly inhibited kidney CaOx deposition and suppressed CaOx-induced renal tubular cell inflammatory injury and necrosis in a CaOx nephrocalcinosis mouse model. Furthermore, RvD1 and PD1 facilitated the expression of the oxidative indicator superoxide dismutase 2 (SOD2), inhibited NADPH oxidase 2 (NOX2) expression, and diminished intracellular reactive oxygen species (ROS) levels. This study preliminarily elucidated the role of lipids in kidney stones. The inhibitory effects of RvD1 and PD1 on oxidative damage induced by CaOx deposition provide a promising perspective for kidney stone treatment strategies.