大飞扬草外泌体纳米囊泡调控Nrf2/HO-1/NQO1通路改善对乙酰氨基酚诱导肝损伤的机制研究 点击下载
| 论文标题： | 大飞扬草外泌体纳米囊泡调控Nrf2/HO-1/NQO1通路改善对乙酰氨基酚诱导肝损伤的机制研究 |
| 英文标题： | |
| 中文摘要： | 目的 基于核因子E2相关因子（Nrf2）/血红素加氧酶1（HO-1）/醌氧化还原酶1（NQO1）通路，探讨大飞扬草外泌体纳米囊泡（Eh-ENVs）对对乙酰氨基酚（APAP）诱导肝损伤的改善作用及机制。方法通过考察Eh-ENVs对RAW264.7和AML12细胞活力的影响，以及对正常小鼠血清肝、肾功能指标和肝、肺等组织病理形态学的影响，评价其安全性。构建脂多糖（1μg/mL）诱导的RAW264.7细胞炎症模型，考察10、20μg/mLEh-ENVs对模型细胞中炎症因子mRNA表达和活性氧（ROS）水平的影响，并考察RAW264.7细胞对Eh-ENVs的摄取效率。构建APAP诱导的肝损伤小鼠模型，考察4mg/kgEh-ENVs对模型小鼠血清肝功能指标，肝组织病理形态学，肝组织中炎症因子mRNA表达、丙二醛（MDA）水平、超氧化物歧化酶（SOD）水平以及Nrf2/HO-1/NQO1通路相关mRNA及其蛋白表达的影响。结果体外实验结果显示，Eh-ENVs对RAW264.7和AML12细胞均无增殖抑制作用；Eh-ENVs可被RAW264.7细胞高效摄取，并能显著降低细胞中白细胞介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）mRNA表达和ROS水平（P＜0.05）。体内实验结果显示，4mg/kgEh-ENVs对正常小鼠无明显毒副作用；可显著降低模型小鼠血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平（P＜0.05），上调/升高肝组织中IL-10mRNA以及Nrf2、HO-1、NQO1mRNA及其蛋白表达和SOD水平（P＜0.05），下调/降低肝组织中TNF-α、IL-1βmRNA表达和MDA水平（P＜0.05）。结论Eh-ENVs可能通过激活Nrf2/HO-1/NQO1通路，抑制炎症反应并减轻氧化应激，进而改善APAP诱导的肝损伤。 |
| 英文摘要： | OBJECTIVE To investigate the ameliorative effect and mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles（Eh-ENVs） on acetaminophen （APAP）-induced liver injury based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H：quinone oxidoreductase 1 （NQO1） pathway. METHODS The safety of Eh-ENVs was evaluated by examining their effects on the viability of RAW264.7 and AML12 cells， as well as serum liver and kidney function indicators and histopathology of liver， lung， and other tissues in normal mice. A lipopolysaccharide （1 μg/mL）-induced RAW264.7 cell inflammation model was constructed to investigate the effects of 10 and 20 μg/mL Eh-ENVs on the mRNA expression of inflammatory factors and reactive oxygen species （ROS） level in model cells， and the uptake efficiency of Eh-ENVs by RAW264.7 cells was also examined. An APAP-induced liver injury mouse model was established to investigate the effects of 4 mg/kg Eh-ENVs on serum liver function indicators， liver histopathology， mRNA expression of inflammatory factors， malondialdehyde （MDA） level， superoxide dismutase （SOD） level， and mRNA and protein expressions related to the Nrf2/HO-1/NQO1 pathway in liver tissue of model mice. RESULTS In vitro results showed that Eh-ENVs had no inhibitory effect on the proliferation of RAW264.7 and AML12 cells；Eh-ENVs could be efficiently taken up by RAW264.7 cells and significantly reduced the mRNA expression of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and ROS level in cells （ P ＜0.05）. In vivo results showed that 4 mg/kg Eh-ENVs had no obvious toxic side effects on normal mice，could significantly decrease the serum alanine transaminase （ALT） and aspartate transaminase （AST） levels in model mice （ P ＜0.05），upregulated/increased the mRNA expressions of IL-10， as well as the mRNA and protein expressions of Nrf2， HO-1， and NQO1， and SOD level in liver tissue （ P ＜0.05）， and down-regulated/decreased the mRNA expression of TNF-α， IL-1β and MDA level in liver tissue （ P ＜0.05）. CONCLUSIONS Eh-ENVs may activate the Nrf2/HO-1/NQO1 pathway to inhibit inflammatory response and alleviate oxidative stress， thereby improving APAP-induced liver injury. |
| 期刊： | 2026年第37卷第09期 |
| 作者： | 王炎玉；陈磊；刘仁杰；乡世健；周本杰 |
| 英文作者： | WANG Yanyu，CHEN Lei，LIU Renjie，XIANG Shijian，ZHOU Benjie |
| 关键字： | 大飞扬草；外泌体纳米囊泡；药物性肝损伤；氧化应激；Nrf2/HO-1/NQO1通路；对乙酰氨基酚 |
| KEYWORDS： | Euphorbia hirta L.； exosome-like nanovesicles； drug-induced liver injury； oxidative stress； Nrf2/HO-1/NQO1 |
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