【摘要】 目的 通过自身前后对照研究观察临床验方心肾缓衰方改善慢性肾脏病合并心力衰竭（CKD-HF）患者心肾功能的临床疗效，并基于非靶向代谢组学比较经治肾功能改善预后不同人群的基线代谢组学差异。方法 选取2023年6月—2023年12月就诊于中国中医科学院广安门医院肾病科门诊的CKD-HF患者36例，在西医常规一体化治疗的基础上，予心肾缓衰方治疗12周，收集患者估算肾小球滤过率（eGFR）、氨基末端脑钠肽前体（NT-proBNP）等理化指标，并比较中医证候积分和明尼苏达生活质量量表评分，以进行客观和主观疗效评价，同时基于超高效液相色谱串联质谱（UHPLC/MS）代谢组学分析临床队列中16例（每组8例）经治肾功能改善预后不同患者的基线代谢差异。结果 共有33例患者完成随访，经心肾缓衰方治疗后eGFR改善（P<0.01），其改善总有效率为69.70%;NT-proBNP、明尼苏达生活质量评价积分下降（P<0.05,P<0.01），中医证候积分下降（P<0.01），其改善总有效率为72.73%；对血清样本进行非靶向代谢组学分析，筛选得到37种差异性代谢物，结果显示色氨酸、精氨酸等氨基酸代谢物及不饱和游离脂肪酸、中链酰基肉碱等脂质与CKD-HF不良预后相关，进一步通过差异性代谢物通路富集阐述CKD-HF生理病理机制，分析发现CKD-HF经治肾功能改善预后不同患者中脂肪酸生物合成等12条通路异常。结论 心肾缓衰方对改善CKD-HF患者的心肾功能具有积极意义，能延缓肾功能进展，改善临床症状，提高患者生活质量，同时预后不同人群的基线氨基酸、脂质等代谢差异明显，其中脂肪酸生物合成通路显著富集。更多还原

【Abstract】 Objective To observe the clinical efficacy of Xinshen Huanshuai Formula in improving cardiac and renal function in patients with chronic kidney disease complicated by heart failure(CKD-HF) through a self-controlled study, and to compare baseline metabolomic differences in patients with different renal prognoses using non-targeted metabolomics.Methods Thirty-six CKD-HF patients who attended the Department of Nephrology at Guang’anmen Hospital, China Academy of Chinese Medical Sciences, from June to December 2023, were enrolled. On the basis of standard integrated Western therapy, all patients received Xinshen Huanshuai Formula for 12 weeks. Clinical outcomes were assessed by physicochemical indicators such as estimated glomerular filtration rate(eGFR) and N-terminal pro-B-type natriuretic peptide(NT-proBNP), traditional Chinese medicine(TCM) syndrome scores, and Minnesota Living with Heart Failure Questionnaire(MLHFQ) scores to provide objective and subjective evaluations. Metabolomic profiling using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry(UHPLC-MS/MS) was performed on baseline serum samples from 16 patients(8 per group) stratified by renal prognosis to analyze metabolic differences.Result Thirty-three patients completed follow-up. After 12 weeks of treatment with Xinshen Huanshuai Formula, eGFR significantly improved(P < 0. 01), with a total effective response rate of 69. 70%. NT-proBNP and MLHFQ scores decreased significantly(P < 0. 05 and P < 0. 01, respectively), and TCM syndrome scores also decreased(P < 0. 01), with a total effective rate of 72. 73%. Nontargeted metabolomics analysis identified 37 differential metabolites. Amino acid metabolites, including tryptophan and arginine, as well as lipids such as unsaturated free fatty acids and medium-chain acylcarnitines, were associated with poor CKD-HF prognosis. Pathway enrichment analysis revealed 12 dysregulated pathways, including fatty acid biosynthesis, reflecting the underlying pathophysiological mechanisms of CKD-HF in patients with different renal prognoses.Conclusion Xinshen Huanshuai Formula effectively improves cardiac and renal function in CKD-HF patients, delays renal function deterioration, alleviates clinical symptoms, and enhances quality of life. Significant baseline differences in amino acid and lipid metabolism exist between patients with different renal prognoses, with marked enrichment of the fatty acid biosynthesis pathway.更多还原