目的 探究胸腺素β4（thymosin beta 4, Tβ4）对BV2小胶质细胞焦亡的保护作用及分子机制。 方法 将BV2细胞分为对照组（不作任何处理）、焦亡组［1 μg/mL脂多糖（lipopolysaccharide, LPS）刺激12 h后，给予10 μmol/L尼日利亚菌素（Nigericin, Nig）处理1 h］、Tβ4处理组（同步给予LPS、Nig后，1 μg/mL Tβ4处理1 h）。通过LPS联合Nig处理BV2小胶质细胞，构建脓毒症相关性脑病体外模型。采用CCK‑8法检测Tβ4对BV2细胞的细胞活力，反转录实时荧光定量PCR法检测白细胞介素（interleukin, IL）‑1β、干扰素诱导蛋白四肽重复序列1、β干扰素mRNA表达水平，酶联免疫吸附试验检测细胞上清液中IL‑1β水平，Western blot法检测NOD样受体热蛋白结构域相关蛋白3、消皮素D N端片段、切割型胱天蛋白酶1、磷酸化干扰素基因刺激因子、磷酸化干扰素调节因子3蛋白表达水平，流式细胞术结合碘化丙啶染色检测细胞死亡率，MitoSOX荧光指示剂检测细胞线粒体活性氧水平。 结果 与焦亡模型组比较，Tβ4处理组BV2细胞焦亡形态损伤减轻，细胞内IL‑1β、干扰素诱导蛋白四肽重复序列1、β干扰素mRNA表达与细胞上清IL‑1β含量、NOD样受体热蛋白结构域相关蛋白3、消皮素D N端片段、切割型胱天蛋白酶1、磷酸化干扰素基因刺激因子、磷酸化干扰素调节因子3蛋白表达及细胞死亡率、线粒体活性氧水平降低（P0.05）。 结论 Tβ4可改善LPS+Nig诱导的BV2小胶质细胞焦亡损伤，抑制氧化应激与炎症反应，其机制可能与cGAS‑STING信号通路有关。

Objective To investigate the protective effects and molecular mechanisms of thymosin β4 (Tβ4) on pyroptosis in BV2 microglial cells. Methods BV2 cells were divided into three groups: control group (no treatment), pyroptosis group [stimulated with 1 μg/mL lipopolysaccharide (LPS) for 12 hours, followed by 10 μmol/L nigericin (Nig) treatment for 1 hour], and Tβ4 treatment group (co-incubated with LPS and Nig, then treated with 1 μg/mL Tβ4 for 1 hour). An in vitro sepsis-associated encephalopathy model was established by LPS and Nig co-treatment. Viability of BV2 cells was assessed by CCK-8 assay. RT-qPCR was performed to detect mRNA expression of interleukin (IL)-1β, interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), and interferon-β (IFN-β). IL-1β levels in cell supernatants were measured by ELISA. Protein expression of NLRP3, GSDMD-N, cleaved caspase-1, phosphorylated stimulator of interferon genes (p-STING), and phosphorylated interferon regulatory factor 3 (p-IRF3) was analyzed by Western blot. Cell death rate and mitochondrial reactive oxygen species (ROS) levels were detected by flow cytometry using propidium iodide staining and MitoSOX indicator, respectively. Results Compared with the pyroptosis group, Tβ4 treatment alleviated morphological damage caused by pyroptosis in BV2 cells. Intracellular mRNA expression of IL-1β, IFIT1, and IFN-β; IL-1β concentration in supernatant; protein expression of NLRP3, GSDMD-N, cleaved caspase-1, p-STING, and p-IRF3; cell death rate; and mitochondrial ROS levels were significantly decreased (P0.05). Conclusions Tβ4 protects BV2 microglial cells against LPS and Nig-induced pyroptosis by inhibiting oxidative stress and inflammatory responses, potentially through regulation of the cGAS-STING signaling pathway.