肝硬化伴临床显著门脉高压患者的门静脉血浆脂质组学研究  

A study on lipidomic profiling of portal vein plasma in cirrhotic patients with clinically significant portal hypertension

作　　者：张瀚文 吴俊嶺 赵志壮 陈怡 栾哲 孙刚 ZHANG Hanwen;WU Junling;ZHAO Zhizhuang;CHEN Yi;LUAN Zhe;SUN Gang(Department of Gastroenterology,the First Medical Center of the Chinese PLA General Hospital,Beijing 100080;Department of Geriatric Medicine,Chinese PLA General Hospital Hainan Branch,China)

机构地区：[1]中国人民解放军总医院第一医学中心消化内科,北京100080 [2]中国人民解放军总医院海南医院老年医学科

出　　处：《胃肠病学和肝病学杂志》2024年第5期578-584,共7页Chinese Journal of Gastroenterology and Hepatology

基　　金：国家自然科学基金项目(32170898)。

摘　　要：目的研究肝硬化伴临床显著门脉高压(clinically significant portal hypertension,CSPH)患者的门静脉血浆脂质组学特征。方法以2021年2月至2023年5月于中国人民解放军总医院第一医学中心就诊的26例肝硬化患者为研究对象,介入下取得门静脉血浆样本,依据肝静脉压力梯度(hepatic vein pressure gradient,HVPG)分为CSPH组(HVPG≥10 mmHg)和非CSPH组(HVPG<10 mmHg),利用超高效液相色谱/质谱(ultra high performance liquid chromatography/mass spectrometry,UPLC/MS)平台对两组患者样本进行脂质组学分析,使用主成分分析(principal component analysis,PCA)和正交偏最小二乘法判别分析(orthogonal partial least squares discriminant analysis,OPLS-DA)对数据进行多变量统计分析,以VIP>1,P<0.05且FC>1.5或<1/1.5为界值筛选差异脂质代谢物。结果CSPH组Hb、血小板和血清白蛋白低于非CSPH组,Child-Pugh评分高于非CSPH组,差异有统计学意义(P<0.05);两组患者性别、年龄、BMI等人口学信息及Hb、血小板和血清白蛋白之外的临床指标比较,差异均无统计学意义(P>0.05);PCA分析及OPLS-DA分析显示两组样品脂质组成模式存在差别;共筛选出48个差异脂质代谢物,包括肉毒碱、神经酰胺、半乳糖神经酰胺、溶血磷脂酰乙醇胺、磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰甘油、磷脂酰肌醇等。结论UPLC/MS平台可有效筛选出肝硬化伴临床显著门脉高压患者与非临床显著门脉高压患者中的差异脂质代谢物。该发现为充分理解肝硬化病程中的代谢改变提供了新的视野,为潜在的诊断治疗靶点发掘提供了理论依据。Objective To elucidate the lipidomic profiles in the portal vein plasma of cirrhotic patients with clinically significant portal hypertension(CSPH).Methods A cohort of 26 cirrhotic patients from the First Medical Center of the Chinese PLA General Hospital from Feb.2021 to May 2023 was included in the study.Interventional procedures were employed to obtain portal vein plasma samples.Patients were stratified into CSPH group(HVPG≥10 mmHg)and non-CSPH group(HVPG<10 mmHg).Lipidomic analyses were conducted on the samples by the ultra high performance liquid chromatography/mass spectrometry(UPLC/MS)platform.Principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were applied as multivariate statistical approaches.Selection of differential lipid metabolites adhered to predefined criteria,including VIP>1,P<0.05,and FC>1.5 or<1/1.5.Results The CSPH group displayed significantly diminished levels of Hb,platelets and serum albumin in comparison to the non-CSPH group,and a notably higher Child-Pugh score than the non-CSPH group,demonstrating statistical significance(P<0.05).Extensive comparisons of demographic parameters,spanning gender,age,BMI and various clinical indicators beyond Hb,platelets and serum albumin revealed no statistically significant differences between the two groups(P>0.05).PCA and OPLS-DA analyses unveiled distinctive variations in lipid composition patterns between the two groups.A comprehensive identification of 48 differential lipid metabolites ensued,encompassing compounds such as carnitine,ceramide,lactosylceramide,lysophosphatidylethanolamine,phosphatidylcholine,phosphatidylethanolamine,phosphatidylglycerol and phosphatidylinositol.Conclusion The UPLC/MS platform can effectively screen differential lipid metabolites between patients with clinically significant portal hypertension in cirrhosis and those without clinically significant portal hypertension.This discovery provides a new perspective for understanding metabolic changes in the course of cirrhosis

关 键 词：肝硬化 临床显著门脉高压 门静脉 血浆 脂质组学 

分 类 号：R575[医药卫生—消化系统]