知识与财富的链接
医用及工业纳米材料的环境健康效应评价及其潜在生物安全性研究已成为纳米生物学及预防医学领域的研究热点。本研究拟探讨氨基修饰的四氧化三铁纳米颗粒(amino-modified iron oxide nanoparticles, NH2-Fe3O4NPs)尾静脉单次5 mg·kg-1给药1周后对非酒精性脂肪性肝炎(nonalcoholic steatohepatitis, NASH)模型小鼠肝脏功能及疾病进展的影响。本研究首先合成生物相容性好的NH2-Fe3O4NPs,利用透射电子显微镜(transmission electron microscopy, TEM)、扫描电子显微镜(scanning electron microscopy, SEM)和动态光散射(dynamic light scattering, DLS)等技术表征其表面形貌结构、粒径分布、zeta电位、水合粒径等物理化学性质。接着,将24只C57BL6/J小鼠随机分为4组,分别为等量磷酸盐缓冲液(phosphate buffer saline, PBS)给药组(对照组)、NH2-Fe3O4NPs尾静脉单次5 mg·kg-1给药1周正常小鼠组(暴露组)、蛋氨酸-胆碱缺乏饮食(methionine- and choline-deficient, MCD)诱导组(NASH模型组)、NH2-Fe3O4NPs尾静脉单次5 mg·kg-1给药NASH模型小鼠1周暴露组(NASH模型暴露组)。研究结果表明,NH2-Fe3O4NPs暴露正常健康小鼠,引起小鼠轻微的肝损伤;NH2-Fe3O4NPs暴露NASH模型小鼠,引起肝脏铁沉积并加重MCD饮食诱导的小鼠肝脏损伤,如提高血清生化指标丙氨酸转氨酶(alanine aminotransferase, ALT)和天门冬氨酸氨基转移酶(aspartate aminotransferase, AST)水平,激活固醇调节元件结合蛋白-1c (sterol regulatory element-binding protein-1c, SREBP-1c)介导的肝脏脂肪从头合成代谢,引起肝脏脂滴沉积和氧化应激,加剧肝脏组织病理学损伤,促进肝脏炎症反应和肝纤维化。综上,本研究发现,相比正常健康小鼠,NH2-Fe3O4NPs暴露加重MCD饮食诱导的小鼠肝脏脂肪变性、炎症反应、肝纤维化和肝脏损伤,加速NASH小鼠疾病进展。本研究结果将为纳米材料的生物医学应用,特别是对NASH这一患病群体的生物学效应与安全性评价机制提供重要的实验支撑和理论依据。
The increasing application of nanomaterials on biomedical and industrial fields have raised public concerns to assess their potential effect on environment and public health. This present study aims to explore the effects of amino-modified iron oxide nanoparticles (NH2-Fe3O4NPs) on the pathogenesis and progress of nonalcoholic steatohepatitis (NASH) in mice. The morphology and size of the synthesized NH2-Fe3O4NPs were characterized by transmission electron microscopy (TEM), scanning EM (SEM), zeta potential, and dynamic light scattering (DLS). Then we explored the hepatic effects of biocompatible NH2-Fe3O4NPs against methionine- and choline-deficient (MCD) diet-induced NASH mice. Compared with healthy mice, NH2-Fe3O4NP exposure significantly increased hepatic iron accumulation and aggravated MCD-induced hepatic steatosis and liver injury in mice, including higher levels of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic oxidative stress, sterol regulatory element-binding protein-1c (SREBP-1c)-mediated de novo lipogenesis, and liver fibrosis. This study provides the evidence that it is necessary to consider the potential hepatic effect of nanomaterial exposure on the clinical pathogenesis and progression of NASH.
