Abstract：Objective: To investigate the mechanism by which long non-coding RNA (LncRNA) nuclear enriched abundant transcript 1 (NEAT1) promotes the expression of formyl peptide receptor 2 (FPR2) and affects the pro-inflammatory phenotype and pyroptosis of macrophages in septic rats. Methods: A cecal ligation and puncture (CLP) method was used to establish a sepsis rat model. Fifty-six SD rats were randomly divided into 7 groups (n=8 per group): Sham surgery group, Sepsis group, Sepsis + Empty vector group, Sepsis + Overexpression LncRNA NEAT1 group, Sepsis + Negative control silencing group, Sepsis + Silencing lncRNA NEAT1 group, and Sepsis + Silencing lncRNA NEAT1 + Recombinant human FPR2 (rhFPR2) group. Lung tissue pathological changes were observed by H&E staining. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of lncRNA NEAT1. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of interleukin-18 (IL-18), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage fluid. Flow cytometry was used to detect the CD86+ subpopulation ratio of macrophages. Western blot analysis was performed to detect the expression of FPR2, NLR family pyrin domain containing 3 (NLRP3), and cleaved-caspase1. Electron microscopy was used to observe the pyroptosis of alveolar macrophages. Results: Compared to the sham surgery group, the sepsis group showed significant upregulation in the expression of LncRNA NEAT1, FPR2, IL-18, IL-1β, CD86+ macrophage subpopulation, TNF-α, iNOS, NLRP3, and cleaved-caspase1 (all P<0.05). Lung tissue showed severe inflammatory cell infiltration, alveolar swelling, bleeding, and marked macrophage pyroptosis. Compared to the sepsis + empty vector group, the sepsis + overexpression lncRNA NEAT1 group showed significant upregulation in the above indicators (all P<0.05). Compared to the sepsis + negative control silencing group, the sepsis + silencing lncRNA NEAT1 group showed significant downregulation in the above indicators (all P<0.05), with reduced lung tissue inflammatory cell infiltration, alveolar swelling, bleeding, and decreased pyroptosis. Compared to the sepsis + silencing lncRNA NEAT1 group, the sepsis + silencing lncRNA NEAT1 + rhFPR2 group showed significant upregulation in FPR2, IL-18, IL-1β, CD86+ macrophage subpopulation, TNF-α, iNOS, NLRP3, and cleaved-caspase1 (all P<0.05), with aggravated lung tissue inflammatory cell infiltration, alveolar swelling, bleeding, and increased pyroptosis. Conclusion: lncRNA NEAT1 aggravates the pro-inflammatory phenotype and pyroptosis of sepsis macrophages in rats by upregulating FPR2 expression, thereby intensifying the inflammatory response and tissue damage in sepsis.
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2025, Vol. 31 
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