目的 探究高血压性心肌肥厚(hypertensive cardiac hypertrophy, HCH)发病机制与四味土木香散 (siwei tumuxiang powder, STP)的治疗机制。方法 采用腹主动脉缩窄术(Abdominal Aortic Coarctation surgery,AAC)诱导高血压性心肌肥厚大鼠模型,将SD大鼠随机分为假手术(Sham)组、模型(Mod)组、四味土木香散(STP)组、阳性药卡托普利(Cap)组,12周后对各组大鼠进行尾动脉压检测、超声心动图检测、HE、Masson染色和代谢组学检测。结果 与假手术组相比,Mod组大鼠血压升高、心室壁增厚、心功能减弱,心肌组织出现病理性损伤和纤维化,在给予STP后有所缓解,且STP药效与阳性药Cap之间无明显差异；代谢组学结果显示,Sham组与Mod组之间共鉴定出143种代谢差异物、Mod组与STP组之间共鉴定出108种代谢差异物,并鉴定出HCH代谢差异物12个；KEGG分析结果显示HCH的发病与Fc epsilon RI信号通路、组氨酸代谢、甘氨酸、丝氨酸和苏氨酸代谢、血清素能突触、脂肪酸生物合成这5种代谢通路有有关,且在STP干预后可通过不饱和脂肪酸的生物合成、脂肪酸生物合成、胆汁分泌这3种代谢通路治疗HCH。结论 HCH的发病机制可能与脂质代谢和氨基酸代谢相关,且STP可以通过影响脂肪酸代谢与胆汁分泌治疗HCH。

Objective: Investigate the pathogenesis and therapeutic mechanism of hypertensive cardiac hypertrophy (HCH) and Siwei Tumuxiang Powder (STP). Methods: Hypertensive cardiac hypertrophy (HCH) was induced in rats through Abdominal Aortic Coarctation surgery (AAC). Rats were randomly divided into Sham, Mod, STP, and positive drug Captopril (Cap) groups. After 12 weeks, tail artery pressure, echocardiography, HE staining, Masson staining, and metabolomics were conducted. Results: Compared with the Sham group, rats in the Mod group showed elevated blood pressure, increased ventricular wall thickness, decreased cardiac function, pathological damage, and fibrosis in myocardial tissue. These effects were alleviated after STP treatment, and there was no significant difference in efficacy between STP and the positive drug Captopril. Metabolomics results revealed 143 identified differential metabolites between the Sham and Mod groups, 108 between the Mod and STP groups, and 13 differential metabolites associated with HCH. KEGG analysis indicated the involvement of Fc epsilon Rl signaling pathway, histidine metabolism, glycine, serine and threonine metabolism, serotonin synapse, and fatty acid biosynthesis in the pathogenesis of HCH. Furthermore, after STP intervention, these pathways could be modulated through unsaturated fatty acid biosynthesis, fatty acid biosynthesis, and bile secretion for the treatment of HCH. Conclusion: The pathogenesis of HCH may be associated with lipid metabolism and amino acid metabolism, and STP can treat HCH by influencing fatty acid metabolism and bile secretion.

R541

国家自然科学基金地区项目(82360095), 内蒙古自治区科技计划(2020GG0238), 内蒙古自治区高等学校创新团队发展计划(NMGIRT2420)