Zhang Zhanpeng, Fan Bin, Zhou Changyu, Zhang Peipei, Liu Chuanming, Xiang Ying, Xia Weinian, Sun Guogen, You Yufeng, Li Dezhong, Xu Jianqiang, Huang Jiaqiang, Huang Chuying
Hubei Minzu University Affiliated Enshi Clinical Medical School, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Selenium and Human Health Institute, the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China.
Hubei Provincial Key Lab of Selenium Resources and Bioapplications, Enshi, 445000, China.
Adv Healthc Mater. 2025 Jul;14(19):e2500467. doi: 10.1002/adhm.202500467. Epub 2025 Jun 5.
Metabolic dysfunction-associated steatohepatitis (MASH) is a prevalent chronic liver disease characterized by steatosis, hepatitis, and fibrosis. Despite its global impact, a standardized clinical treatment protocol remains undeveloped. In this study, novel selenium nanoparticles (SeNPs) are synthesized using Lactobacillus coryniformis ES23 (L. coryniformis ES23). It is found that SeNPs significantly mitigate liver steatosis, inflammation, and fibrosis induced by a choline-deficient, L-amino-acid-defined, high-fat diet (CDAHFD). Mechanistically, SeNPs regulate fatty acid and triglyceride metabolism through the peroxisome proliferator-activated receptor alpha (PPARα) pathway. Moreover, these results show that SeNPs maintain iron homeostasis by reducing the expression of heme oxygenase 1 (HMOX1) and transferrin receptor (TFRC), therefore decreasing iron accumulation and inhibiting ferroptosis in the mouse liver. Taken all, the findings in this study suggest that SeNPs can serve as a novel therapeutic approach for treating MASH via modulating lipid metabolism and ferrous ion homeostasis.
代谢功能障碍相关脂肪性肝炎（MASH）是一种常见的慢性肝病，其特征为脂肪变性、肝炎和纤维化。尽管它具有全球影响，但标准化的临床治疗方案仍未制定出来。在本研究中，使用棒状乳杆菌ES23（L. coryniformis ES23）合成了新型硒纳米颗粒（SeNPs）。研究发现，SeNPs能显著减轻由胆碱缺乏、L-氨基酸限定的高脂饮食（CDAHFD）诱导的肝脏脂肪变性、炎症和纤维化。从机制上讲，SeNPs通过过氧化物酶体增殖物激活受体α（PPARα）途径调节脂肪酸和甘油三酯代谢。此外，这些结果表明，SeNPs通过降低血红素加氧酶1（HMOX1）和转铁蛋白受体（TFRC）的表达来维持铁稳态，从而减少铁积累并抑制小鼠肝脏中的铁死亡。综上所述，本研究结果表明，SeNPs可作为一种通过调节脂质代谢和亚铁离子稳态来治疗MASH的新型治疗方法。
