目的 探究心可舒片缓解斑马鱼高脂血症的作用，并初步阐明其分子机制。方法 利用0.05%蛋黄粉喂养诱导的斑马鱼模型结合油红O染色评价心可舒片（100、200、400 μg·mL^-1）的调血脂作用，并检测总超氧化物歧化酶（T-SOD）活性以及丙二醛（MDA）、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）的含量。联合网络药理学、转录组学、分子对接分析心可舒片的潜在调脂机制；实时荧光定量PCR（qRT-PCR）技术检测肿瘤坏死因子（TNF）和磷脂酰肌醇3-激酶（PI3K）-蛋白激酶B（Akt）信号通路中akt1、akt2、caspase3、sele、mapk14、pik3r1基因表达量和转录组学筛选的差异基因ncf1、gpr84、irf1b、noxo1a、zgc:92275、crx、flvcr2a、serping1、ccl20a.3、bcl3、rpll3a的表达量进行验证。结果 与模型组比较，心可舒片能够显著缓解高脂喂食导致的斑马鱼体内脂质积累，降低TC、TG、LDL-C和MDA含量，增强T-SOD活性（P＜0.01）。网络药理学、分子对接及qRT-PCR验证结果表明，心可舒片主要作用于ALB、Akt1、IGF1、EGFR、CASP3和MMP9等靶点，通过调控TNF和PI3K-Akt信号通路缓解高脂血症。转录组学及qRT-PCR验证结果表明，戊糖磷酸途径和吞噬作用在心可舒片的调脂过程中也发挥着关键作用。结论 心可舒片可以缓解斑马鱼高脂血症及伴随的氧化应激，作用机制与TNF、PI3K-Akt信号通路及其调控的炎症和代谢途径有关。

Objective To investigate the effect of Xinkeshu Tablets on alleviating hyperlipidemia in zebrafish and preliminarily elucidate its molecular mechanism. Methods The lipid-regulating effects of Xinkeshu Tablets (100, 200, and 400 μg·mL^-1) were evaluated using a zebrafish model induced by 0.05% egg yolk powder feeding, combined with Oil Red O staining, and the activities of total superoxide dismutase (T-SOD), as well as the levels of malondialdehyde (MDA), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), were measured. Potential lipid-regulating mechanisms of Xinkeshu Tablets were further analyzed through integrated network pharmacology, transcriptomics, and molecular docking. Real-time quantitative PCR (qRT-PCR) was employed to validate the expression levels of genes involved in the tumor necrosis factor (TNF) and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathways—specifically akt1, akt2, caspase3, sele, mapk14, and pik3r1—as well as differentially expressed genes identified by transcriptomics, including ncf1, gpr84, irf1b, noxo1a, zgc:92275, crx, flvcr2a, serping1, ccl20a.3, bcl3, and rpl13a. Results Compared with the model group, Xinkeshu Tablets significantly alleviated lipid accumulation in zebrafish induced by a high-fat diet, reduced levels of TC, TG, LDL-C, and MDA, and enhanced T-SOD activity (P<0.01). Network pharmacology, molecular docking, and qRT-PCR validation results indicated that Xinkeshu Tablets primarily target ALB, Akt1, IGF1, EGFR, CASP3, and MMP9, ameliorating hyperlipidemia by modulating the TNF and PI3K-Akt signaling pathways. Transcriptomics and qRT-PCR validation further revealed that the pentose phosphate pathway and phagocytosis also play crucial roles in the lipidregulating effects of Xinkeshu Tablets. Conclusion Xinkeshu Tablets alleviates hyper-lipidemia and its associated oxidative stress in zebrafish, with its lipid-lowering mechanism involving the TNF, PI3K-Akt signaling pathway and the inflammatory and metabolic pathways it regulates.

R965

国家自然科学基金联合基金项目（U23A20514）；齐鲁工业大学（山东省科学院）科教产融合试点工程重大创新专项（2025ZDZX14）；山东省中医药科技项目（M20242212）；外专双百项目（WSR2024032，WSP2024016）；国家高端人才项目（H20240744）；国家药品监督管理局药品审评中心重点实验室开放课题（2021TREDP01）；山东生物健康食品高值开发利用技术创新中心重大创新任务（SDJSZX2025ZDRW03）