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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Effect of rapamycin nanoparticles in an animal model of primary biliary cholangitis
Yu-Shu Yang, Xian-Rui Li, Zhi-Min Wang, Lin Zheng, Jin-Long Li, Xiao-Lin Cui, Yan-Biao Song, Jun-Ji Ma, Hui-Fang Guo, Li-Xia Gao, Xiao-Hui Zhou
Yu-Shu Yang, Zhi-Min Wang, Jin-Long Li, Xiao-Lin Cui, Hui-Fang Guo, Li-Xia Gao, Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Xian-Rui Li, College of Pharmacy, Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Zhi-Min Wang, Department of Rheumatology and Immunology, The Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China
Lin Zheng, Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Yan-Biao Song, Central Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Jun-Ji Ma, Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang 050000, Hebei Province, China
Xiao-Hui Zhou, School of Food and Biology, Hebei University of Science and Technology, Shijiazhuang 050000, Hebei Province, China
Co-first authors: Yu-Shu Yang and Xian-Rui Li.
Co-corresponding authors: Li-Xia Gao and Xiao-Hui Zhou.
Author contributions: Yang YS and Li XR contributed equally to this work, contributed to methodology, formal analysis, data extraction, preparation of rapamycin nanoparticles and editing; Wang ZM contributed to data extraction, data curation; Zheng L, Li JL and Cui XL contributed to animal rearing, specimen collection and treatment; Song YB and Ma JJ were involved in guidance of pathological methods; Guo HF was involved in methodology and supervision; Gao LX contributed to conceptualization, funding acquisition, methodology and editing; Zhou XH contributed to nanoparticle design and experimental idea design; all authors have read and approved the final version to be published.
Supported by Cultivation Project of Hebei Natural Science Foundation-Precision Medicine Joint Fund, No. H2021206239.
Institutional animal care and use committee statement: All mice were housed in the specific pathogen-free-grade breeding room of the Experimental Animal Center of The Second Hospital of Hebei Medical University (22 °C, 55% humidity, and 12-hours day-night cycle) and were raised in strict accordance with the animal ethics requirements of the Experimental Animal Center of The Second Hospital of Hebei Medical University.
Conflict-of-interest statement: All the authors declare no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All the authors share the data.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Li-Xia Gao, MD, PhD, Chief Physician, Professor, Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei Province, China.
27100287@ hebmu.edu.cn
Received: December 16, 2024
Revised: February 24, 2025
Accepted: May 21, 2025
Published online: June 27, 2025
Processing time: 192 Days and 3.8 Hours
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 lymphocytes and B lymphocytes in the liver were significantly reduced, with statistically significant differences (24.21% ± 6.55% vs 15.98% ± 3.03%, P < 0.05; 9.09% ± 1.91% vs 5.49% ± 1.00%, P < 0.001; 80.51% ± 2.96% vs 75.31% ± 4.34%, P < 0.05). The expression of CD8+ T lymphocytes and B lymphocytes in the ImmTOR treatment group also decreased (9.09% ± 1.91% vs 5.49% ± 1.00%, P < 0.001; 80.51% ± 2.96% vs 75.31% ± 4.34%, P < 0.05). The liver pathology of PBC mice in the treatment group showed reduced inflammation and a decreased total pathology score, and the difference in the scores was statistically significant (4.50 ± 2.88 vs 1.75 ± 1.28, P < 0.05).
CONCLUSION
ImmTOR can improve biochemistry and pathology of liver obvious by inhibiting the expression of CD8+ T cells and B cells, and reducing the titer of AMA.
Core Tip: Primary biliary cholangitis (PBC) is a chronic autoimmune-mediated cholestatic liver disease, which can gradually progress to liver fibrosis, cirrhosis. The global incidence of PBC has been increasing year by year in recent decades. But there are few effective drugs, the effect of nanoparticles encapsulating rapamycin on the treatment of PBC using an animal model is examined in this paper, targeting at new approaches for the treatment of PBC.
