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Effect of rapamycin nanoparticles in an animal model of primary biliary cholangitis

作者:Yu-Shu Yang, Xianrui Li, Zhimin Wang, Lin Zheng, Jin‐Long Li, Xiao-Lin Cui, Yanbiao Song, Junji Ma, Huifang Guo, Lixia Gao, Xiaohui Zhou · 发表于:World Journal of Hepatology · 年份:2025 · DOI:10.4254/wjh.v17.i6.104073 · 被引用次数:2 · 研究领域:Liver Diseases and Immunity、Liver physiology and pathology、Drug Transport and Resistance Mechanisms

BACKGROUND Primary biliary cholangitis (PBC) is a chronic autoimmune-mediated cholestatic liver disease. Nanoparticles encapsulating rapamycin (ImmTOR) suppress adaptive immune responses and induce the hepatic tolerogenic immune response. AIM To investigate the effects of ImmTOR in PBC mouse models. METHODS PBC models were induced in C57BL/6 mice by two immunizations of 2-octynoic acid-coupled bovine serum albumin at two-week intervals, and polycytidylic acid every three days. The PBC mouse models were separated into the treatment group and the control group. The levels of alkaline phosphatase (ALP) and alanine aminotransferase in the mice were detected using an automatic biochemical analyzer. Liver and spleen mononuclear cells were analyzed by flow cytometry, and serum anti-mitochondrial antibodies (AMA) and the related cytokines were analyzed by enzyme-linked immunosorbent assay. Liver histopathology was examined by hematoxylin and eosin staining and scored. RESULTS After treatment with ImmTOR, the ALP level was significantly decreased (189.60 U/L ± 27.25 U/L vs 156.00 U/L ± 17.21 U/L, P < 0.05), the level of AMA was reduced (1.28 ng/mL ± 0.27 ng/mL vs 0.56 ng/mL ± 0.07 ng/mL, P < 0.001) and the expression levels of interferon gamma and tumor necrosis factor α were significantly decreased (48.29 pg/mL ± 10.84 pg/mL vs 25.01 pg/mL ± 1.49 pg/mL, P < 0.0001) and (84.24 pg/mL ± 23.47 pg/mL vs 40.66 pg/mL ± 14.65 pg/mL, P < 0.001). The CD4+ T lymphocytes, CD8+ T lymp...