目的 探究降香新黄酮 latifolin 通过调控巨噬细胞代谢对急性心肌梗死（AMI）小鼠的作用及机制。 方法 （1）将 50 只雄性 ICR 小鼠随机分为对照组、模型组、美托洛尔组（17.5 mg·kg-1 ）及 latifolin 低、高剂量组 （5、20 mg·kg-1 ），每组 10 只。采用异丙肾上腺素（10 mg·kg-1 ）皮下注射 14 d（每日 1 次）复制 AMI 小鼠模型。 各组尾静脉注射给药，每日 1 次，连续 2 周。采集小鼠心电图数据，包括心率、QTC 间期、QRS 时限及 ST 段 偏移量；采用 ELISA 法检测小鼠血清肌酸激酶 MB 同工酶（CK-MB）、心肌肌钙蛋白Ⅰ（cTn-Ⅰ）、同型半胱氨 酸（HCY）的水平，以及心脏组织白细胞介素 1β（IL-1β）、白细胞介素 6（IL-6）、肿瘤坏死因子 α（TNF-α）的含 量；HE 染色法观察心脏组织病理变化。（2）采用 2.5 ng·mL-1 干扰素 γ（IFN-γ）+200 ng·mL-1 脂多糖（LPS）刺激 RAW264.7 细胞 12 h，复制炎症细胞模型。将 RAW264.7 细胞分为对照组、模型组及 latifolin 低、中、高剂量 组（5、10、20 μg·mL-1 ），干预 24 h。采用 CCK-8 法检测细胞活力；RT-qPCR 法检测细胞 TNF-α、IL-1β、 IL-6、PI3K、AKT1、NF-κB mRNA 表达水平；采用 HPLC-MS 技术检测 RAW264.7 细胞内代谢物的含量；通 过分子对接技术探究 latifolin 与 PI3K、AKT1、NF-κB 靶蛋白的结合能力。结果 （1）与对照组比较，模型组小 鼠的心率、QTC 间期、QRS 时限及 ST 段偏移量均显著提高（P＜0.01）；血清 CK-MB、cTn-Ⅰ、HCY 水平及心 脏组织中 IL-1β、IL-6、TNF-α 水平显著升高（P＜0.01）；心肌纤维断裂，有大量炎性巨噬细胞浸润。与模型 组比较，latifolin 高剂量组小鼠的心率、QRS 时限及 ST 段偏移量显著降低（P＜0.05，P＜0.01）；latifolin 低、高 剂量组小鼠的血清 CK-MB、cTn-Ⅰ、HCY 水平均显著降低（P＜0.05，P＜0.01）；各给药组小鼠心脏组织 中 IL-1β、IL-6 水平显著降低（P＜0.01），latifolin 高剂量组小鼠心脏组织中 TNF-α 水平显著降低（P＜0.01）； 心肌纤维溶解现象及炎性巨噬细胞浸润减少。（2）5～20 μg·mL-1浓度的 latifolin 对 RAW264.7 细胞活力均无明显 影响（P＞0.05）。与对照组比较，模型组 RAW264.7 细胞的 IL-1β、IL-6、TNF-α、PI3K、AKT1、NF-κB mRNA 表达水平均显著升高（P＜0.01），细胞代谢物 S-腺苷甲硫氨酸、L-同型半胱氨酸的含量显著升高 （P＜0.05，P＜0.01）。与模型组比较，latifolin 中、高剂量组 RAW264.7 细胞的 IL-1β、IL-6、TNF-α、PI3K、 AKT1、NF-κB mRNA 表达水平均显著降低（P＜0.01），代谢物 S-腺苷甲硫氨酸、L-同型半胱氨酸含量显著降 低（P＜0.01），L-胱硫醚含量显著升高（P＜0.01）。代谢组学分析发现，latifolin 能显著回调 20 种生物标志物， 主要涉及半胱氨酸和蛋氨酸代谢通路。分子对接结果表明，latifolin 与 PI3K、AKT1、NF-κB 均对接良好。 结论 降香新黄酮 latifolin 能够减轻 AMI 小鼠心肌梗死后的心肌损伤及炎症，可能是通过调控巨噬细胞半胱氨 酸和蛋氨酸代谢，抑制 PI3K/AKT/NF-κB 信号通路来发挥抗 AMI 的作用。

Objective To explore the effect and mechanism of latifolin from the Dalbergiae Odoriferae Lignum against acute myocardial infarction （AMI） in mice by regulating macrophage metabolism. Methods （1） Fifty male ICR mice were randomly divided into control，model，Metoprolol （17.5 mg·kg-1 ），and latifolin low- （5 mg·kg-1 ） and high-dose （20 mg·kg-1 ） groups，with 10 mice per group. An AMI model was established by subcutaneous injection of isoproterenol （10 mg·kg-1 ） for 14 days. Drugs were administered via tail vein injection once daily for 2 consecutive weeks. Electrocardiographic parameters （heart rate， QTC interval， QRS duration， ST-segment deviation） were recorded. Serum levels of creatine kinase-MB （CK-MB），cardiac troponin I （cTn-I），and homocysteine （HCY），as well as cardiac tissue levels of interleukin-1β（IL-1β），IL-6，and tumor necrosis factor-α（TNF-α），were measured by ELISA. Cardiac histopathology was assessed by HE staining.（2） RAW264.7 cells were stimulated with 2.5 ng·mL-1 interferon-γ （IFN-γ） + 200 ng·mL-1 lipopolysaccharide （LPS） for 12 hours to establish an inflammatory model. Cells were divided into control，model，and latifolin low- （5 μg·mL-1 ），medium- （10 μg·mL-1 ），and high-dose （20 μg·mL-1 ） groups for 24 hour. Cell viability was assessed by CCK-8 assay. mRNA expression of TNF-α，IL-1β，IL-6，PI3K，AKT1， and NF-κB was measured by RT-qPCR. Intracellular metabolites were quantified by HPLC-MS. Molecular docking was performed to evaluate latifolin’s binding affinity with PI3K，AKT1，and NF-κB. Results （1） On the whole animal level，compared with the control group，the heart rate，QTC interval，QRS duration and ST segment offset of the model group were significantly increased （P＜0.01）；the serum levels of CK-MB，cTn-I and HCY were significantly increased （P＜0.01）； the contents of IL-1β， IL-6 and TNF- α in myocardial tissue of mice were significantly increased （P＜0.01）. The myocardial fibers of mice were broken and a large number of macrophages infiltrated. Compared with model group， the heart rate， QRS duration and ST segment offset in latifolin high-dose group were significantly decreased （P＜0.05， P＜0.01）. The serum levels of CK-MB， cTn-I and HCY were significantly decreased （P＜0.05， P＜0.01）. The contents of IL-1β， IL-6 and TNF- α in myocardial tissue of mice were significantly decreased （P＜0.01），and the level of TNF-α in the heart tissue of mice in the high-dose latifolin group was significantly decreased （P＜0.01 ）. Myocardial fiber dissolution and inflammatory macrophage infiltration were decreased.（2） Latifolin at concentrations of 5–20 μg·mL-1 had no significant effect on RAW264.7 cell viability （P＞ 0.05）. Compared with the control group，the model group exhibited significantly elevated mRNA expression levels of IL-1β，IL-6，TNF-α，PI3K，AKT1，and NF- κB （P＜0.01），along with increased levels of the metabolites S-adenosylmethionine （SAM） and L-homocysteine （P＜0.05， P＜0.01）. Compared with the model group， the medium- and high-dose latifolin groups showed significantly reduced mRNA expression of TNF- α， IL-1β， IL-6， PI3K，AKT1，and NF-κB （P＜0.01），decreased levels of SAM and L-homocysteine （P＜0.01），and increased L-cystathionine levels （P＜0.01）. Metabolomic analysis revealed that latifolin significantly modulated 20 biomarkers， primarily involved in cysteine and methionine metabolism pathways. Molecular docking results indicated strong binding affinity between latifolin and PI3K， AKT1， and NF- κB. Conclusion Latifolin mitigates myocardial injury and inflammation after myocardial infarction in AMI mice， likely by regulating macrophage cysteine and methionine metabolism and inhibiting the PI3K/AKT/NF-κB pathway.

国家自然科学基金项目（82160761）;江西省自然科学基金项目（20224BAB216106）;江西省中医药管理局科技计划项目（2021B622）;江西省卫生健康委科技计划项目（202211414）;江西中医药大学博士科研启动基金项目（2020BSRW004）;江西中医药大学校级研究生创新专项（JZYC23S73）;中药药理江西重点实验室项目（2024SSY07111）。