输血依赖型地中海贫血患者6个月n-乙酰半胱氨酸干预后血浆脂质组学特征与心脏代谢疾病的相关性：一项前瞻性队列研究

IF 2.3 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry Pub Date : 2025-12-01 Epub Date: 2025-10-22 DOI:10.1016/j.clinbiochem.2025.111030

Yubin Lei , Anik Forest , Caroline Daneault , Ying Liu , Kostas Pantopoulos , Adisak Tantiworawit , Arintaya Phrommintikul , Siriporn Chattipakorn , Nipon Chattipakorn , Christine Des Rosiers , Gary Sweeney

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引用次数: 0

摘要

反复输血引起的铁失衡导致氧化应激是输血依赖型地中海贫血（TDT）患者心脏代谢并发症的主要原因。n -乙酰半胱氨酸（NAC）是一种谷胱甘肽前体，是一种众所周知的抗氧化剂，通过减轻氧化应激对细胞代谢的影响而实现心脏保护作用。目前的研究旨在通过关注先前报道的TDT患者血浆脂质组的变化来评估六个月NAC干预的效果。设计与方法将62例泰国TDT患者随机分为两组：两组均接受6个月的鸡尾酒治疗，包括标准化输血和铁螯合剂治疗，干预组在此基础上每天口服600 mg NAC，对照组接受安慰剂。使用质谱法进行血浆脂质组学分析，评估339例先前注释的TDT患者显著改变的脂质特征。在干预前后测量临床参数，包括心率变异性（HRV）。结果snac治疗显著改变了152项血脂特征（P < 0.03），安慰剂组也改变了78项血脂特征。重要的是，29种脂质特征（26种独特的脂质）在NAC治疗后恢复到健康控制水平。在这个亚群中，循环二酰基甘油磷酸胆碱PC（14:0_20:4）和胆固醇酯CE 18:3与HRV呈正相关，而HRV是nac治疗患者的临床指标。结论6个月口服NAC干预可改变TDT患者的血浆脂质组学特征，部分恢复可能被慢性氧化应激破坏的脂质种类。观察到的nac反应性脂质与HRV改善之间的相关性提示潜在的心脏保护作用。这些发现强调了NAC作为辅助治疗减轻TDT患者心脏代谢并发症的潜力。

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Correlation of plasma lipidomic profiles with cardiometabolic disease in transfusion-dependent thalassemia patients with six-month N-acetylcysteine intervention: A prospective cohort study

Objectives

Oxidative stress, driven by iron imbalance from recurrent blood transfusions, is a major contributor to cardiometabolic complications in transfusion-dependent thalassemia (TDT). N-acetylcysteine (NAC), a glutathione precursor, is a well-known antioxidant with cardioprotective effects achieved by mitigating the impact of oxidative stress on cell metabolism. Current study aimed to evaluate the effect of a six-month NAC intervention by focusing on previously reported changes in the plasma lipidome in TDT patients.

Design & Methods

A randomized cohort of 62 Thai TDT patients was divided into two groups: both received six months of cocktail therapy involving standardized blood transfusions and iron chelator therapy, with the intervention group additionally receiving 600 mg oral NAC daily and the control group receiving a placebo. Plasma lipidomic profiling was performed using mass spectrometry to assess 339 previously annotated lipid features significantly altered in TDT patients. Clinical parameters, including heart rate variability (HRV), were measured before and after the intervention.

Results

NAC treatment significantly altered 152 plasma lipid features (P < 0.03), 78 of which were also altered in the placebo group. Importantly, 29 lipid features (26 unique lipids) were restored toward healthy control levels following NAC treatment. Within this subset, circulating diacylglycerophosphocholines PC(14:0_20:4) and cholesteryl ester CE 18:3 positively correlated with HRV, a clinical marker markedly improved in NAC-treated patients.

Conclusions

Six-month oral NAC intervention modified the plasma lipidomic profile in TDT patients, partially restoring lipid species likely disrupted by chronic oxidative stress. The observed correlation between NAC-responsive lipids and improved HRV suggests a potential cardioprotective effect. These findings highlight the potential of NAC as an adjunctive therapy to mitigate cardiometabolic complications in TDT.

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来源期刊

Clinical biochemistry 医学-医学实验技术

CiteScore

5.10

自引率

0.00%

发文量

151

审稿时长

25 days

期刊介绍： Clinical Biochemistry publishes articles relating to clinical chemistry, molecular biology and genetics, therapeutic drug monitoring and toxicology, laboratory immunology and laboratory medicine in general, with the focus on analytical and clinical investigation of laboratory tests in humans used for diagnosis, prognosis, treatment and therapy, and monitoring of disease.