妊娠合并甲状腺功能减退症患者血浆脂质组学分析及临床意义

Plasma Lipomics Analysis and Clinical Significance of Patients with Hypothyroidism During Pregnancy

目的:分析妊娠合并甲状腺功能减退症(简称甲减)患者的血浆脂质代谢变化及临床意义。方法:选择2019年9月至2020年4月于郑州大学第三附属医院建档并分娩的30例妊娠合并甲减患者(病例组)和30例正常孕妇(对照组)的临床资料和妊娠结局,采用液相色谱串联质谱(LC-MS/MS)法分析两组孕妇脂质代谢谱的差异,并用KEGG富集分析筛选差异代谢物参与的关键通路,酶联免疫吸附(ELISA)法验证特定差异代谢物。结果:①与对照组相比,病例组孕妇的血清C反应蛋白(CRP)水平显著升高,新生儿体质量显著降低(P<0.05);②LC-MS/MS分析共鉴定出55个差异脂质代谢物,涉及甘油磷脂代谢、致病性大肠杆菌感染和自噬等代谢通路(P<0.05);③采用多元变量统计分析,选取磷脂酰胆碱(PC)、溶血磷脂酰胆碱(LPC)和磷脂酰乙醇胺(PE)为潜在生物标志物,ELISA验证其差异有统计学意义(P<0.05);④PC、LPC、PE水平与促甲状腺激素(TSH)呈正相关,与游离甲状腺素(FT 4)水平呈负相关,且PC与CRP水平呈正相关,LPC、PE水平与新生儿出生体质量呈负相关,较高的PC、LPC、PE水平与早产、低出生体质量儿、胎膜早破的风险增加独立相关(P<0.05)。结论:妊娠合并甲减的脂质代谢谱及代谢通路存在差异化表达,且与不良妊娠结局相关,在疾病的诊治和机制探索中具有一定作用。

Objective:To analyze the changes and clinical significance of plasma lipid metabolism in pregnant patients with hypothyroidism.Methods:The study recorded clinical data and pregnancy outcomes of 30 pregnant patients with hypothyroidism(case group)and 30 normal pregnant women(control group)who delivered at our hospital between September 2019 and April 2020.The differences in lipid metabolism profiles between two groups of pregnant women were analyzed by liquid chromatography-tandem mass spectrometry(LC-MS/MS).We identified key pathways involved in the differential metabolites utilizing KEGG enrichment analysis and validated specific differential metabolites using enzyme-linked immunosorbent assay(ELISA).Results:①The study found that pregnant women in the case group had significantly higher serum C-reactive protein(CRP)levels and lower newborn weight compared to the control group(P<0.05);②LC-MS/MS analysis revealed 55 differential lipid metabolites,involving metabolic pathways,such as glycerol phospholipid metabolism,pathogenic escherichia coli infection and autophagy(P<0.05);③Multivariate statistical analysis was used to identify potential biomarkers,with phosphatidylcholine(PC),lysophosphatidylcholine(LPC)and phosphatidylethanolamine(PE)being selected as statistically significant biomarkers,as confirmed by ELISA(P<0.05);④The levels of PC,LPC and PE were positively correlated with the levels of thyroid hormone(TSH),and were negatively correlated with the levels of free thyroid hormone(FT4).There was a positive correlation between the levels of PC and CRP,and a negative correlation between the levels of LPC,PE and the weight of newborns.The higher levels of PC,LPC and PE were independently associated with an increased risk of preterm birth,low birth weight infants,and premature rupture of membranes(P<0.05).Conclusions:There was a notable difference in the lipid metabolism profile and metabolic pathways of pregnant women with hypothyroidism,which was linked to adverse pregnancy outcomes,providing a new basis for the study of the diagnosis,treatment and pathogenesis of hypothyroidism during pregnancy.