Nephrolithiasis causes severe pain and is a highly recurrent pathophysiological state. Calcium-containing stones, specifically calcium oxalate (CaOx), is the most common type accounting for approximately 75 % of stone composition. Genetic predisposition, gender, geographic region, diet, and low fluid intake all contribute to disease pathogenesis. However, exposure to environmental pollutants as a contribution to kidney stone formation remains insufficiently studied. Lead (Pb2+) is of particular interest as epidemiological data indicate that low-level exposure (BLL = 0.48–3.85 μM) confers a 35 % increased risk of developing CaOx nephrolithiasis. However, mechanisms underlying this association have yet to be elucidated. Drosophila melanogaster provide a useful genetic model where major molecular pathophysiological pathways can be efficiently studied. Malpighian tubules (MT) were isolated from either Wild-Type or InsP₃R knockdown flies and treated with oxalate (5 mM) ± Pb²⁺ (2μM) for 1 h. Following exposure, MTs were imaged and crystals quantified. CaOx crystal number and total area were significantly increased (˜5-fold) in Pb²⁺(pre-treatment) + oxalate-exposed MTs when compared to oxalate alone controls. However, CaOx crystal number and total crystal area in Pb²⁺ + oxalate-exposed InsP₃R knockdown MTs were significantly decreased (˜3-fold) indicating the role for principal cell-specific InsP₃R-mediated Ca²⁺ mobilization as a mechanism for Pb²⁺-induced increases in CaOx crystallization inset model of nephrolithiasis.

肾结石会引起剧烈疼痛并且是一种高度复发的病理生理状态。含钙结石，特别是草酸钙 (CaOx)，是最常见的类型，约占结石成分的 75%。遗传易感性、性别、地理区域、饮食和低液体摄入量都有助于疾病的发病机制。然而，暴露于环境污染物对肾结石形成的贡献仍未得到充分研究。铅 (Pb2+) 是特别令人感兴趣的，因为流行病学数据表明，低水平暴露（BLL = 0.48–3.85 μM）会使发生 CaOx 肾结石的风险增加 35%。然而，这种关联的潜在机制尚未阐明。果蝇提供一个有用的遗传模型，可以有效地研究主要的分子病理生理学途径。Malpighian 小管 (MT) 从野生型或 InsP ₃ R 敲低果蝇中分离出来，并用草酸盐 (5 mM) ± Pb ²⁺ (2μM) 处理 1 小时。曝光后，对 MT 进行成像并对晶体进行量化。与单独的草酸盐对照相比，Pb ²⁺（预处理）+暴露于草酸盐的 MT 中的CaOx 晶体数量和总面积显着增加（~5 倍）。然而，暴露于 Pb ²⁺ + 草酸盐的 InsP ₃ R 敲低 MT 中的CaOx 晶体数量和总晶体面积显着降低（~3 倍），表明主细胞特异性 InsP ₃ R 介导的 Ca ^{2+ 的作用}动员作为 Pb ²⁺诱导肾结石 CaOx 结晶插入模型增加的机制。