目的 探讨Maresin1（MaR1）通过抑制细胞焦亡减轻下肢缺血再灌注损伤的作用机制。 方法 本研究采用体内外实验相结合。体内实验共使用27只C57BL/6小鼠随机分为对照组（Control组）、模型组（LL-IRI组）和治疗组（MaR1组）。造模成功并药物干预后，取各组5例（n = 5）小鼠腓肠肌组织进行转录组测序与生物信息学分析；其余样本用于评估组织病理损伤、检测toll样受体4（TLR4）/核因子-κB（NF-κB）p65及核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）/Gasdermin-D（GSDMD）蛋白表达；试剂盒测定采集后的小鼠血清中MDA含量及CAT活性。体外实验采用LPS联合ATP刺激L6骨骼肌细胞构建焦亡模型，分组造模后行ELISA检测各组细胞上清IL-1β与IL-18含量。 结果 BulkRNA测序分析提示，与对照组相比，LL-IRI组中TLR4/NF-κB/NLRP3信号通路以及细胞焦亡相关基因表达显著上调，经MaR1干预后可逆转以上趋势，并负向调控炎症小体活化与细胞焦亡相关生物学过程。组织病理切片显示LL-IRI 组肌纤维排列紊乱、断裂明显，免疫荧光佐证生信分析，TLR4/NF-κBp65与NLRP3/GSDMD的蛋白表达显著增强（P < 0.01），且伴随血清MDA含量升高（P < 0.01）、CAT活性下降（P < 0.01）。MaR1治疗能显著改善上述病理、分子及生化指标。体外实验结果表明LPS+ATP组较正常组相比，焦亡终末炎症因子IL-1β与IL-18的释放水平明显上升（P < 0.01），在MaR1干预后能有效抑制IL-1β与IL-18的释放（P < 0.01）。 结论 MaR1可能通过阻断TLR4/NF-κB/NLRP3炎症级联抑制细胞焦亡，从而减轻小鼠下肢缺血再灌注损伤。

Objective To investigate the mechanism by which Maresin1 reduces lower limb ischemia-reperfusion injury through the inhibition of pyroptosis. Methods This study employed a combination of in vivo and in vitro experiments. In the in vivo experiment， 27 C57BL/6 mice were randomly allocated into the Control group， the model group （LL-IRI）， and the treatment group （MaR1）. After successful modeling and drug intervention， the gastrocnemius muscle tissue of 5 mice （n = 5） from each group was collected for transcriptome sequencing and bioinformatics analysis. The remaining samples were utilized to assess histopathological damage and to detect the expression of TLR4/NF-κB p65 and NLRP3/GSDMD proteins. The MDA content and CAT activity in the serum were determined using kits. In vitro， L6 skeletal muscle cells were stimulated with LPS and ATP to establish a pyroptosis model. After modeling， ELISA was applied to measure the content of IL-1β and IL-18 in the supernatant of each group. Results Bulk RNA sequencing analysis demonstrated that， in comparison with the control group， the TLR4/NF-κB/NLRP3 signaling pathway and the expression of pyroptosis-related genes were significantly up-regulated in the LL-IRI group. Moreover， the intervention of MaR1 could reverse the above-mentioned trend， as MaR1 negatively regulated the activation of inflammasomes and the biological process associated with pyroptosis. Immunohistochemistry indicated that the expression of TLR4/NF-κB p65 and NLRP3/GSDMD was significantly enhanced in the LL-IRI group （P < 0.01）， accompanied by an increase in serum MDA content （P < 0.01） and a decrease in CAT activity （P < 0.01）. MaR1 treatment could significantly improve these pathological， molecular， and biochemical parameters. The results of in vitro experiments showed that， compared with the normal group， there was a significant increase in the release of inflammatory factors IL-1β and IL-18 at the end of pyroptosis in the LPS + ATP group （P < 0.01）. After the intervention of MaR1， the release of IL-1β and IL-18 in the LPS + ATP group was significantly reduced （P < 0.01）. Conclusion MaR1 may inhibit pyroptosis by blocking the TLR4/NF-κB/NLRP3 inflammatory cascade， thereby alleviating lower limb ischemia/reperfusion （I/R） injury in mice.