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Background: Aplastic anemia (AA) is a bone marrow failure disease characterized by immune-mediated destruction of hematopoietic stem and progenitor cells. Bone marrow adiposity represents a typical pathological manifestation observed in AA.
Methods: The aim of this study was to establish a murine model of AA using immune-mediated methods and assess the impact of rapamycin (Rapa) and cyclosporin A (CsA) on bone marrow adiposity. The AA murine model was induced by 137Cs γ-ray irradiation and allogeneic lymphocyte infusion. Rapamycin and cyclosporine were administered intraperitoneally. Hematological parameters, bone marrow adiposity, and lipidomic profiles were evaluated. Gene and protein expression related to adipogenesis were analyzed.
Results: The Hematoxylin and Eosin (HE) and BODIPY staining results revealed an increase in adipocyte area and a decrease in hematopoietic area in AA murine. Relative expression levels of PPAR-γ, LPL, and Ap2 mRNA were significantly elevated in bone marrow mononuclear cells (BMMNCs) from the AA group. Lipidomics analysis indicated notable differences between the AA group and the normal group regarding lipid metabolism, particularly concerning glycerolphospholipids. Following treatment with Rapa and CsA, not only did the hematological profile of AA murine recover, but there was also a reduction in bone marrow adiposity in HE and BODIPY staining and a decrease in the gene and protein expression of PPAR-γ, LPL, and Ap2. The lipidomic analysis revealed a reduction in the lipid metabolism of AA murine following Rapa and CsA treatment in AA murine, particularly acylcarnitin (ACar), phosphatidylserine (PS) and phosphatidylethanolamine (PE). The enrichment results of the KEGG pathway analysis demonstrated a statistically significant role of C42H82N010P in glycerophospholipid metabolism.
Conclusions: Our study used lipidomics for the first time to investigate lipid metabolism in AA murine, revealing that Rapa and CsA primarily downregulate glycerophospholipid metabolism as a means to alleviate bone marrow adiposity in AA murine.
DOI: 10.7754/Clin.Lab.2025.250207
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