目的 探讨牛舌草水提物（AIAE）抗心力衰竭作用及作用机制。方法 以AB野生型及Tg（cmlc2：EGFP）斑马鱼为研究对象，设置对照组、模型（200 μmol∙L⁻¹盐酸维拉帕米）组、地高辛（阳性药，10 μg·mL⁻¹）组、AIAE（0.1、0.5、2.5 mg·mL⁻¹）组。给药后检测各组斑马鱼心包面积、静脉淤血面积、静脉窦-动脉球（SV-BA）距离、心率、短轴缩短率（FS）、射血分数（LVEF）、血流速度变化；吖啶橙染色观察心肌细胞凋亡，苏木素-伊红（HE）染色观察心脏组织病理变化；试剂盒法检测钠尿肽系统中N末端脑钠肽前体（NT-proBNP）含量；实时荧光定量PCR（qRT-PCR）法检测脑钠肽（bnp）及心钠肽（anp）mRNA表达水平。通过转录组测序（RNA-seq）预测AIAE抗心力衰竭的相关信号通路，并利用qRT-PCR检测信号通路相关基因的表达水平。结果 与模型组相比，AIAE组斑马鱼心包面积、静脉淤血面积、SV-BA距离均显著减小（P＜0.05、0.01、0.001），心肌细胞凋亡数减少，心率、FS、LVEF、血流速度显著升高（P＜0.05、0.01、0.001），心脏壁厚度有不同程度恢复，NT-proBNP含量、bnp、anp mRNA表达水平显著降低（P＜0.05、0.01、0.001）。RNA-seq结果提示AIAE可能通过调控氧化磷酸化、糖酵解/糖异生等能量代谢相关通路发挥作用。qRT-PCR验证结果表明AIAE可调控上述通路cox6a1、pck1等基因的异常表达（P＜0.05、0.01、0.001）。结论 AIAE通过调节氧化磷酸化、糖酵解/糖异生等信号通路，抑制钠尿肽系统激活，抑制心肌细胞凋亡发挥抗心力衰竭作用。

Objective To investigate the effect and possible mechanism of aqueous extract of Anchusa italica (AIAE) on heart failure in zebrafish. Methods Zebrafish of AB wild type and Tg (cmlc2: EGFP) were used as research subjects. The control group, model group (200 μmol∙L⁻¹ verapamil hydrochloride), digoxin group (positive drug, 10 μg·mL⁻¹), and AIAE groups (0.1, 0.5, 2.5 mg·mL⁻¹) were set up. After administration, the pericardial area, venous congestion area, distance between sinus venosus and bulbus arteriosus (SV-BA), heart rate, fractional shortening (FS), left ventricular ejection fraction (LVEF), and blood flow velocity changes of zebrafish in each group were detected. Acridine orange staining was used to observe myocardial cell apoptosis, and hematoxylin-eosin (HE) staining was used to observe pathological changes in cardiac tissue. The content of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the natriuretic peptide system was detected by kit method. The mRNA expression levels of brain natriuretic peptide (bnp) and atrial natriuretic peptide (anp) were detected by real-time fluorescence quantitative PCR (qRT-PCR). The related signaling pathways of AIAE in anti-heart failure were predicted by transcriptome sequencing (RNA-seq), and the expression levels of related genes in the signaling pathways were detected by qRT-PCR. Results Compared with the model group, the pericardial area, venous congestion area, SV-BA distance, NT-proBNP content, bnp and anp mRNA expression levels were significantly reduced (P < 0.05, 0.01, 0.001), the number of cardiomyocyte apoptosis was reduced, the heart rate, FS, LVEF and blood flow velocity were significantly increased (P < 0.05, 0.01, 0.001), and the heart wall thickness was restored to different degrees in the AIAE groups. RNA-seq results suggested that AIAE may play a role in regulating oxidative phosphorylation, glycolysis/gluconeogenesis and other energy metabolism-related pathways. qRT-PCR results showed that AIAE could regulate the abnormal expression of cox6a1, pck1 and other genes in this pathway (P < 0.05, 0.01, 0.001). Conclusion The AIAE plays an anti-heart failure role by regulating oxidative phosphorylation, glycolysis/gluconeogenesis and other signaling pathways, inhibiting the activation of NP system and inhibiting cardiomyocyte apoptosis.

R285.5

中央引导地方科技发展专项资金项目（ZYYD2024JD06）；天山创新团队项目（2024D14018）；新疆维吾尔自治区重点实验室开放课题（KLUMH-202404）