高血压脑出血术后痰瘀腑实证血浆代谢组学的检测分析

目的从代谢组学层面寻找高血压脑出血术后痰瘀腑实证的本质以及通腑泻热活血合剂治疗作用机制。方法采用氢谱磁共振(1 H-NMR)CPMG脉冲序列检测12例高血压脑出血患者的术前及术后第1、3、7、12天血浆样本,每例患者采集5个血浆样本,本实验共收集60个血样本,所有患者的术前、术后第1天、术后第3天、术后第7天、术后第12天各为1组,分为5组,所有患者术后第3天开始服用通腑泻热合剂。对不同组之间代谢产物含量的变化,采用主成分分析(principal components analysis,PCA)、偏最小二乘判别分析(PLS-discriminant analysis,PLSDA),对比观察5组血浆中的磁共振波谱差异情况,分析相应的代谢产物积分值变化情况。最终选择对本次实验贡献值最大的代谢物,将此代谢物和自身前后进行比对,随后运用统计学方法进行检验,对比不同组别之间的血浆代谢物变化差异。结果患者术前、术后第1天、术后第3天、术后第7天、术后第12天中5组血浆代谢谱在对比中出现差异,且具有统计学意义(P0.05),在模式识别和主成份进行分析中,结果表明高血压脑出血术后第3天痰瘀腑实证形成,服用通腑泻热合剂前后具有可区分性、可比较性;术前组和术后第1天组患者血浆中差异较大的特异性代谢物6个:丙氨酸、异亮氨酸、α-酮戊二酸、糖蛋白、前列腺素、极低密度脂蛋白。术后第1天组和术后第3天组中患者血浆中差异较大的特异性代谢物6个:γ-氨基丁酸、α-酮戊二酸、甜菜碱、丝氨酸、前列腺素E1、脂蛋白;术后第3天组和术后第12天组中患者血浆中差异较大的特异性代谢物6个:N-乙酰糖蛋白、α-葡糖糖、胆碱、肌醇、亮氨酸、谷氨酰胺。术后第7天组和术后第12天组中患者血浆中差异较大的特异性代谢物2个:N-乙酰糖蛋白、乳酸。结论当高血压脑出血术后痰瘀腑实证形成,服用通腑泻热活血合剂可以改善脑出血后患者体内脂肪含量,更可以改善血糖代谢,稳定细胞膜等,促进已损伤细胞修复。

Detection analysis of Phlegm and Stasis Fu-organ Syndrome after treatment of hypertensive cerebral hemorrhage through metabonomics

Objective To find out the essence of Phlegm and Stasis Fu-organ Syndrome and the function of mixture for purging diarrhea and activating blood circulation through metabonomics after treatment of hypertensive cerebral hemorrhage.Methods CPMG sequential detection of hydrogennuclear magnetic resonance(1 H-NMR)was applied to test the plasma samples of patients before treatment and one day,seven days and twelve days after treatment of hypertensive cerebral hemorrhage.Five plasma sam-ples were collected from each patient.Sixty plasma samples were collected for this research in total.There were five groups:plasma samples before treatment,one day,three days,seven days and twelve days after treatment.All the patients were asked to take the mixture for purging diarrhea and activating blood circulation.Content changes of metabolite in different groups were ana-lyzed through principal components analysis(PCA)and PLS-discriminant analysis (PLSDA).NMR difference of the five groups of plasma samples and integral value of relevant metabolite were also analyzed.Metabolite with the greatest contribution for the re-search was chosen at last.Results Difference of plasma metabolization profiling in the five groups was statistically significant with (P <0.05).During the analysis process of pattern recognition and principal components,it was found that Phlegm and Stasis Fu-organ Syndrome formed three days after treatment.The results were distinguishable and comparable before and after taking mix-ture for purging diarrhea and activating blood circulation.There were six specific metabolites in the pre-operation group and the group one day after operation.They were alanine,isoleucine,α-oxoglutarate,glycoprotein,prostaglandin and very low density lipo-protein.There were six specific metabolites in the groups one day and three days after operation.They wereγ-aminobutyric acid,α-oxoglutarate,betaine,serine,prostaglandin-E1 and lipoprotein.There were also six specific metabolites in the groups three days and twelve days after operation.They were N-glycoprotein,α-glucose,choline,inositol,leucine and glutamine.There were two specific metabolites in the groups seven days and twelve days after operation.They were N-glycoprotein and lactate.Conclusion When Phlegm and Stasis Fu-organ Syndrome forms after treatment of hypertensive cerebral hemorrhage,taking mixture for purging di-arrhea and activating blood circulation can improve fat content and metabolism of the patients.It can also stabilize patients'cy-tomembrane and help injured cells recover.