基于网络毒理学及分子对接方法探索短链 增塑剂对肾结石发生作用机制的影响

Exploring the Impact of Short-Chain Plasticizers on the Mechanisms of Kidney Stone Formation Based on Network Toxicology and Molecular Docking Approaches

摘要: 邻苯二甲酸二乙酯(DEP)、邻苯二甲酸二异丁酯(DiBP)和邻苯二甲酸丁基苄酯(BBZP)等增塑剂是普遍存在的环境污染物，与多种不良健康效应相关。然而，它们与肾结石病的关联及其潜在机制仍不清楚。本研究采用网络毒理学、分子对接的综合方法，阐明这些增塑剂对肾结石发病机制的影响。网络毒理学为每种增塑剂确定了五个关键蛋白靶点(例如，AKT1、SRC、EGFR、EP300)，这些靶点主要参与调节细胞生长和代谢的信号转导。分子对接证实了增塑剂与这些靶点之间存在稳定的结合相互作用。总之，我们的研究结果提供了新的见解，表明BBZP和DiBP可能通过干扰对肾细胞功能至关重要的细胞信号通路来促进肾结石的形成。这项研究强调了重新评估常用增塑剂安全性的必要性，并突出了减轻全球肾结石负担的潜在干预策略。

Abstract: Plasticizers such as diethyl phthalate (DEP), Diisobutyl phthalate (DiBP), and butyl benzyl phthalate (BBZP) are ubiquitous environmental pollutants associated with various adverse health effects. However, their association with kidney stone disease and the underlying mechanisms remain unclear. This study employed an integrated approach of network toxicology and molecular docking to elucidate the effects of these plasticizers on the pathogenesis of kidney stones. Network toxicology identified five key protein targets for each plasticizer (e.g., AKT1, SRC, EGFR, EP300), which are primarily involved in signal transduction regulating cell growth and metabolism. Molecular docking confirmed stable binding interactions between the plasticizers and these targets. In conclusion, our findings provide novel insights suggesting that BBZP and DiBP may contribute to kidney stone formation by interfering with cellular signaling pathways crucial for renal cell function. This research underscores the need to reassess the safety of commonly used plasticizers and highlights potential intervention strategies to mitigate the global burden of kidney stones.