As a widely used lipid lowering agent, simvastatin recently has been frequently detected in aquatic environment and the potential adverse effects from simvastatin exposure to non-target organisms such as fish is worthy of more attention. The aim of this study was to reveal the responses of detoxification system in fish to simvastatin exposure. In this investigation a ubiquitous small freshwater fish, mosquito fish (Gambusia affinis), was employed as test organism, and the transcriptional expression of nucleus transcriptional factor pregnane X receptor (PXR) and its downstream genes, including P-glycoprotein (P-gp), cytochrome 3A (CYP3A), multidrug resistance protein 2 (MRP2), UDP-glucuronosyl transferase (UGT) in mosquito fish were investigated by qRT-PCR methods under the exposure of concentrations of simvastatin (0.5 μg L⁻¹, 5 μg L⁻¹, 50 μgL⁻¹, 500 μg L⁻¹) for 24 h, 72 h and 168 h. The related enzyme activity (Erythromycin-N-Demethylase, ERND), the protein expression of PXR and the histological changes of liver tissues in fish were also determined via west blotting and transmission electron microscope approaches in the same conditions. Results showed that the mRNA expression of PXR, CYP3A and P-gp showed significantly changes under simvastatin exposure, exhibiting an obvious time/dose-effect relationship with the prolong of exposure time. ERND activity also showed time-effect at 24 h, and western blotting showed PXR protein displaying a dose-effect relationship to some extent. Hepatocyte cellular of mosquito fish exposed to simvastatin (5 μg L⁻¹, 168 h) exhibited obvious histological changes in form of swelling, incomplete fragmentary structure etc. Overall, simvastatin altered the expression of PXR signaling pathway and subsequently bring about changes in high-levels of mosquito fish.

辛伐他汀作为一种广泛使用的降脂剂，近年来在水生环境中频繁被检测到，鱼类等非靶标生物暴露于辛伐他汀的潜在不良影响值得更多关注。本研究的目的是揭示鱼类解毒系统对辛伐他汀暴露的反应。本研究以普遍存在的小型淡水鱼蚊鱼（ Gambusia affinis ）为试验生物，研究核转录因子孕烷X受体（PXR）及其下游基因，包括P-糖蛋白（P-gp）的转录表达。在辛伐他汀浓度（0.5 μg L ^-1 、5 μg L ^{-1 ）}暴露下，通过 qRT-PCR 方法研究了蚊鱼中细胞色素 3A (CYP3A)、多药耐药蛋白 2 (MRP2)、UDP-葡萄糖醛酸基转移酶 (UGT) 的变化。 ^{1、50μgL -1} 、500μgL ^-1 )持续24小时、72小时和168小时。在相同条件下，通过Western blotting和透射电镜方法测定鱼体内相关酶活性（红霉素-N-脱甲基酶，ERND）、PXR蛋白表达以及肝组织的组织学变化。结果表明，辛伐他汀暴露后PXR 、 CYP3A 、 P-gp mRNA表达量发生显着变化，且随暴露时间的延长呈现明显的时效关系。 24 h时ERND活性也表现出时间效应，Western blotting显示PXR蛋白呈现一定的量效关系。 辛伐他汀暴露(5 μg L ^-1 , 168 h)的蚊鱼肝细胞表现出明显的组织学变化，如肿胀、碎片结构不完整等。总体而言，辛伐他汀改变了PXR信号通路的表达，从而引起高浓度的变化。食蚊鱼的水平。