罗耳阿太菌多糖经Nrf2通路预防小鼠肝脏铅损伤机制

目的:本研究旨在探究罗耳阿太菌多糖（Athelia rolfsii polysaccharides，AEPS）保护铅暴露小鼠肝脏的作用机制。方法:小鼠随机分为正常组（NC）、模型组（MC）、阳性对照组（PC）、AEPS低剂量组（LD）、AEPS中剂量组（MD）、AEPS高剂量组（HD）、全反式维甲酸（all-trans-retinoic acid, ATRA）单独组（ATRA+NC）、ATRA干预组（ATRA+MC）和ATRA+AEPS高剂量组（ATRA+HD）。测定铅暴露小鼠肝脏的铅含量、抗氧化指标、功能指标，苏木伊红染色评估小鼠肝脏病理切片。测定小鼠肝脏谷胱甘肽巯基转移酶（glutathione-s-transferase，GST）活性和谷胱甘肽（glutathione，GSH）水平，肝脏组织中细胞凋亡相关蛋白、多药耐药相关蛋白2（multidrug resistance-associated protein 2，MRP2）及肝细胞核中核因子E2相关因子2（nuclear factor erythroid-2-related factor 2，Nrf2）蛋白水平。结果:AEPS低、中、高剂量组均显著提高铅暴露小鼠肝细胞MRP2运输铅离子的能力（P<0.05），并呈剂量依赖性地减少小鼠肝脏铅积累（P<0.05）。AEPS显著抑制铅暴露小鼠肝细胞凋亡（P<0.05），呈剂量依赖性地增强小鼠肝脏抗氧化能力（P<0.05），恢复肝功能（P<0.05），并减轻肝脏病理损伤。AEPS还促进了Nrf2向肝细胞核转移（P<0.05）。而ATRA干预可降低AEPS对铅暴露小鼠肝脏的保护作用。结论:AEPS依赖于Nrf2信号通路可减少肝脏铅积累，保护肝脏铅损伤。

Mechanism of Athelia rolfsii Polysaccharides Protect against Liver Injury in Lead-Exposed Mice via Nrf2 Signaling Pathway

Objective: The study aimed to explore the mechanism of Athelia rolfsii polysaccharides (AEPS) protected against liver of lead-exposed mice. Methods: Mice were randomly assigned into normal control group (NC), model control group (MC), positive control group (PC), AEPS low dose group (LD), AEPS middle dose group (MD), AEPS high dose group (HD), ATRA alone group (ATRA+NC), ATRA intervention group (ATRA+MC), ATRA+AEPS high dose group (ATRA+HD). Lead levels, antioxidant indexes and functional indexes in the liver of lead-exposed mice were determined, the pathological changes were also evaluated by hematoxylin-eosin (HE) staining. The activity of glutathione-s-transferase (GST) and the levels of glutathione (GSH) were also measured. The protein levels of apoptosis-associated proteins and multidrug resistance-associated protein 2 (MRP2) in liver tissues were determined, as well as nuclear factor erythroid-2-related factor 2 (Nrf2) in liver cell nucleus. Results: Low, middle and high dose of AEPS enhanced the lead ion excretion ability of MRP2 participation, decreased lead accumulation in mice liver significantly in a dose dependent manner (P<0.05). AEPS enhanced antioxidant activity of mice liver (P<0.05), restored liver function (P<0.05), alleviated liver pathological injury induced by lead in a dose dependent manner, as well as suppressed hepatocyte apoptosis of lead-exposed mice significantly (P<0.05). AEPS also promoted Nrf2 nuclear translocation in the liver (P<0.05). However, ATRA reduced the protective efficacy of AEPS on the liver of lead-exposed mice. Conclusion: AEPS reduced lead accumulation in the liver in a Nrf2-dependent manner, and showed liver protective effect.