基于代谢组学的子痫前期发病机制研究

Study on the pathogenesis of preeclampsia based on metabolomics

目的通过代谢组学技术探究子痫前期大鼠血清代谢轮廓的变化,并寻找潜在的疾病诊断标记物,为临床诊治提供参考依据。方法将实验大鼠分为两组:正常妊娠组和子痫前期模型组,其中模型的建立采用皮下注射亚硝基左旋精氨酸甲酯100mg·kg^-1·d^-1建立大鼠子痫前期病理模型,正常妊娠组则同时接受皮下注射生理盐水1.5ml/d,分别注射到妊娠21d。在实验过程中,自孕鼠妊娠第10d开始,每天清晨测量1次尾动脉收缩压,直至分娩为止。并在孕鼠妊娠的第10天和第20天,采用大鼠代谢笼分别收集正常妊娠组和子痫前期组大鼠24h的尿液,用于24h的尿微量蛋白测定。最后将大鼠处死,收集血液样本,用于代谢组学分析。结果血压测量结果显示正当子痫前期组大鼠开始皮下注射亚硝基左旋精氨酸甲酯后,其尾动脉收缩压显著性升高。24h尿蛋白测定结果显示,当给予孕鼠亚硝基左旋精氨酸甲酯后,子痫前期组大鼠的尿蛋白含量显著性高于正常妊娠组。代谢组学分析结果表明子痫前期组大鼠的代谢轮廓与正常大鼠的代谢轮廓发生显著性改变。结论通过多元统计分析并结合ROC曲线分析,总共找到3个潜在的诊断标记物。

Objective To exploRe the changes of seRum metabolic pRofile in Rats with pReeclampsia based on metabolomics,find potential diagnostic maRkeRs,pRovide a RefeRence basis foR clinical diagnosis and tReatment of pReeclampsia. Methods The Rats weRe divided into noRmal pRegnancy gRoup and pReeclampsia model gRoup. Rat model of pReeclampsia was eatablished by subcutaneous injection of nitRo-L-aRginine methyl esteR (100 mg·kg^-1·d^-1 ),the Rats in noRmal pRegnancy gRoup weRe tReated by subcutaneous injection of noRmal saline (1.5ml/d) . The tReatment was continued foR 21 days. In the pRocess of expeRiment,systolic pRessuRe of caudal aRteRy was measuRed fRom the 10th day of pRegnancy to deliveRy,once a day. On the 10th day and the 20th day of pRegnancy,Rat metabolic cage was used to collect uRine samples within 24 houRs in the two gRoups,uRine micRopRotein assay was peRfoRmed. Finally,the Rats weRe sacRificed,then blood samples weRe collected foR metabolomics analysis. Results Blood pRessuRe measuRement showed that blood pRessuRe of the caudal aRteRy incReased significantly afteR subcutaneous injection of nitRo-L-aRginine methyl esteR in pReeclampsia model gRoup; 24-houR uRine micRopRotein assay showed that uRine pRotein content afteR tReatment in pReeclampsia model gRoup was significantly higheR than that in noRmal pRegnancy gRoup. Metabolomics analysis showed that metabolic pRofile of Rats with pReeclampsia changed significantly compaRed with noRmal Rats. Conclusion A total of thRee potential diagnostic maRkeRs weRe found by multivaRiate statistical analysis combined with ROC cuRve analysis.