纳米塑料(NPs)已经成为一种重要的环境污染物,广泛存在于水环境中,并对动物的健康和安全构成严重威胁。骨骼肌,复杂生命活动和功能需求的重要器官,关于NP的影响受到的关注有限。在这项研究中,通过在小鼠中口服不同大小(1mg/kg)的PS-NP来研究聚苯乙烯NP(PS-NP)对骨骼肌发育的影响。研究结果表明,PS-NP导致骨骼肌损伤并显著阻碍肌肉分化,与PS-NP粒径呈负相关。形态学分析显示PS-NP导致肌纤维部分破坏,增加纤维之间的间距,和脂质积累。RT-qPCR和Western印迹分析表明,PS-NP暴露下调了成肌分化相关因子的表达(Myod,Myog和Myh2),激活的PPARγ/LXRβ途径,并上调脂质分化相关因子(SREBP1C,SCD-1,FAS,ACC1,CD36/FAT,ADIPOQ,C/EBPα和UCP-1)。体外实验,C2C12细胞用于确认PS-NP(0、100、200、400μg/mL)通过细胞膜的细胞渗透以及PPARγ表达的激活。此外,为了验证LXRβ是关键的信号分子,沉默RNA转染实验进行,导致PPARγ的表达没有增加,LXRβ,SREBP1C,FAS,CD36/FAT,ADIPOQ,即使暴露于PS-NP后,C/EBPα和UCP-1也是如此。然而,SCD-1和ACC1的表达不受影响。本研究证明,暴露于PS-NP通过PPARγ/LXRβ途径诱导脂质积累,从而影响骨骼肌发育。
Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRβ pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C2C12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 μg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRβ as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRβ, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRβ pathway thereby influencing skeletal muscle development.