Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.

Heat stroke alters hippocampal and cerebellar transmitter metabonomics

BACKGROUND:The mechanisms underlying heat stroke(HS)-induced hippocampal injury remain unclear.This study aimed to evaluate the HS-induced metabonomics of hippocampal and cerebellar transmitters.METHODS:The HS model was established with male Sprague-Dawley rats subjected to heat exposure of up to 42℃ at a humidity of(55.0±5.0)%.The hippocampal and cerebellar transmitters and metabolites of rats were tested via ultra-high-performance liquid chromatography–mass spectrometry(UPLC-MS/MS).The primary transmitters and metabolites were identified by principal component analysis(PCA)and orthogonal partial least square-discriminant analysis(OPLS-DA).The major metabolic pathways for HS were selected after enrichment.The brain injury was evaluated by histological tests.RESULTS:HS induced hippocampal and cerebellar injuries in rats.HS upregulated the protein levels of hippocampal glutamate,glutamine,gamma-aminobutyric acid,L-tryptophan(Trp),5-hydroxy-indoleacetic acid,and kynurenine;however,it downregulated asparagine,tryptamine,5-hydroxytryptophan,melatonin,3,4-dihydroxyphenylalanine(L-DOPA),and vanillylmandelic acid.HS also sharply elevated the protein levels of cerebellar methionine and Trp,and decreased the levels of serotonin,L-alanine,L-asparagine,L-aspartate,cysteine,norepinephrine,spermine,spermidine,and tyrosine.Hippocampal glutamate,monoamine transmitters,cerebellar aspartate acid,and catecholamine transmitters’metabolic pathways were identified as the main metablic pathways in HS.CONCLUSION:The hippocampus and cerebellum were injured in rats with HS,possibly induced the disorder of hippocampal glutamate and serotonin metabolism,cerebellar aspartate acid and catecholamine transmitter metabolism,and related metabolic pathways.

A new metabonomics method for simultaneous determination of EFAs and NEFAs in plasma using GC-MS and its application

A new metabonomics method was developed for simultaneous qualitative and quantitative analysis on esterified and nonesterified fatty acids （EFAs and NEFAs） in plasma. Merely 10 μL of plasma was required. The pretreatment of the sample was simple without disposing the protein. After simple extraction and derivation, 15 FAs in plasma were precisely quantified. Gas chromatography tandem mass spectrometry （GC-MS） was used in the study and the quantities of the analytes, which varied in abundance over three orders of magnitude. The established method showed good accuracy. The curve correlation coefficients were all above 0.997. The RSDs of precision for all compounds were below 15% and recoveries were all between 80 and 110%. PLS-DA modal was used in the data management. 2009 Guo An Luo. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Application of the Reversed-phase Liquid Chromatography Coupled to Ion Trap Mass Spectrometry with Principal Components Analysis for Metabonomics Studies of Scutellarin in Rat Urine

Metabonomics, a novel systemic approach, was applied to studies of Traditional Chinese Medicine scutellarin in rat urine. The liquid chromatography coupled with ion trap mass spectrometry combined with PCA was used in this paper. With this methodology, two potential metabolites of scutellarin were detected and the nine ions responsible for the gender variation and one ion for the dosage variation were found.

Serum Metabonomics of Articular Cartilage Destruction Induced by T-2 Toxin in Wistar Rats

The molecular pathogenesis of T-2 toxin-induced cartilage destruction has not been fully unraveled yet. The aim of this study was to detect changes in serum metabolites in a rat anomaly model with articular cartilage destruction. Thirty healthy male Wistar rats were fed a diet containing T-2 toxin （300 ng/kg chow） for 3 months. Histopathological changes in femorotibial cartilage were characterized in terms of chondrocyte degeneration/necrosis and superficial cartilage defect, and the endogenous metabolite profile of serum was determined by UPLC/Q-TOF MS. Treated rats showed extensive areas of chondrocyte necrosis and superficial cartilage defect in the articular cartilage. In addition, 8 metabolites were found to change significantly in these rats compared to the control group, including lyso PE （18：0/0：0）, lyso PC（14：0）, lyso PC[18：4 （6Z,9Z,12Z,15Z）], lyso PC[（16：1（9Z）], lyso PC（16：0）, L-valine, hippuric acid, and asparaginyl-glycine. These 8 metabolites associated with cartilage injury are mainly involved in phospholipid and amino acid metabolic pathways.

UPLC-Q/TOF-MS based metabonomics revealed protective effect of Terminalia chebula extract on ischemic stroke rats

Terminalia chebula(TC),a kind of Combretaceae,is a widely used herb in India and East Asia to treat cerebrovascular diseases.However,the potential mechanism of the neuroprotective effects of TC at the metabonomics level is still not unclear.The present study focused on the effects of TC on metabonomics in stroke model.In our study,rats were divided randomly into Sham,Model,and TC groups.The TC group were intragastricly administered with TC for 7 d after middle cerebral artery occlusion(MCAO)operation.The sham and the model groups received vehicle for the same length of time.Subsequently,the neuroprotective effects of TC were examined by neurological defects evalua⁃tion,infarct volume assessment,and identification of biochemical indicators for antioxidant and anti-inflammatory activi⁃ties.Further,metabonomics technology was employed to evaluate the endogenous metabolites profiling systematically.Consist to results of biochemical and histopathological assays,pattern recognition analysis showed a clear separation of the Model and the Sham group,indicating a recovery impact of TC on the MCAO rats.Moreover,12 potential biomarkers were identified in MCAO Model group,involved in energy(lactic acid,succinic acid,and fumarate),amino acids(leucine,alanine,and phenylalanine)and glycerophospholipid[PC(16∶0/20∶4),PC(20:4/20:4),LysoPC(18:0)and LysoPC(16:0)]metabolism,and other types of metabolism(arachidonic acid and palmitoylcarnitine).Notably,we found that metabolite levels of TC group were partially reversed to normal.In conclusion,TC could ameliorate MCAO rats by intervening with energy metabolism(glycolysis and TCA cycle),amino acid metabolism,glycerophospholipid metabolism and other types of metabolism.

Metabonomics/metabolomics analysis technology and its application in quality control of traditional Chinese medicines

Chinese medicines are an important part of traditional Chinese medicines,but their'safe,effective,stable and controllable'issue still remains to be solved.The rise of metabonomics in 20th century,consistent with the overall adjustment concept of multi-component,multi-level,multi-target,multi-metabolic pathways of traditional Chinese medicines,is conducive to solve basic problems in their quality control.This paper systematically describes recent application and development of 1H-NMR metabonomics techniques,LC-MS metabonomics techniques and GC-MS metabonomics techniques in the quality control of traditional Chinese medicines.It provides a new reference for Chinese medicines and the identification and quality assessment of their products.

1H-NMR-based Metabolomic approach to evaluating total flavonoids of Ocimum Basilicum Linn in apolipomtein E knockout mice

OBJECTIVE To observe the effects of serum metabolites by using ~1H-NMR-based metabonomic approach to explore the possible mechanisms of total flavonoids in Ocimum BasilicumLinn(OBL) on atherosclerosis in apolipomtein E knockout(ApoE-/-) mice.METHODS Six-week-old male apoE knockout mice were divided into four groups(n=10) and fed with high fet diet:model,Simv.astatin,OBL-H,OBL-M and OBL-L groups.The homogeneous male mice of C57 BL/6 J were used as the normol group and fed with normal chow diet.After 14 weeks,~1H-NMR technology was used to ex.plore the variability of serum metabolites by the method of PLS-DA and OPLS-DA.RESULTS Com.pared with normal group,Model group showed a significant increase in the serum levels of VLDL,LDL,β-hydroxyisobutyrate,lactate,myo-inositol and showed a significant decrease in the serum levels of al.anine,glutamine,proline,carnitine,methylamine,citrate,creatine,choline,taurine,pyruvate,β-glu.cose,α-glucose,glycine,lysine.Combined with model group OBL-H,OBL-M,OBL-L groups showed the effects of regulating the levels of different metabolites of the glucose,lipid and amino acid metabo.lism.CONCLUSION The anti-atheros-clerotic activity of total flavonoids in Ocimum BasilicumLinn may be related not only to regulation of lipid metabolism,but also glycometabolism and amino acid metabolism.

Screening for potential biomarkers of traditional Chinese medicinechest impediment syndromesbased on plasma metabonomics

OBJECTIVE To have a systematic pathomechanism view of three chest impediment.syndromes of Qi Deficiency and Blood Stasis syndrome(QDBS),Qi Stagnation and Blood Stasis syn.drome(QSBS),Cold Obstruction and Qi Stagnation syndrome(COQS) and further investigate the changed metabolome and related pathways for screening potential biomarkers in rat plasma.METHODS According to clinical pathogeny,three kinds of syndrome models were established to simulate the disease of chest impediment.Plasma metabonomics based on UPLC-Q-TOF/MS was applied in this research to detected small molecule metabolites for identifyingthe special potential biomarkers of three chest impediment syndromes,respectively.RESULTS Significant metabolic differences were observed between thecontrol group and three syndrome groups.Furthermore,three syndrome groups were distinguished clearly by pattern recognition method.The particular metabolites contributing most to the classification of three chest impediment syndromes were identified.In the QSBS group,the potential biomarkers could include 2-keto-glutaramic acid,L-methionine,L-homocysteic acid,octadecanamide,stearoylglycine,behenic acid,linoleylcarnitine,lysoPC(14:1(9 Z)),indoxyl sulfate and cholic acid.In the COQS group,they could be aminoadipic acid,palmitic amide,oleamide,lysoPC(P-16:0),lysoPC(P-18:0),lysoPC(20:2(11 Z,14 Z)),9-HETE and tauroursodeoxycholic acid.Moreover,4-pyridoxic acid,L-palmi.toylcarnitine,lysoPC(20:0),lysoPC(22:5(4 Z,7 Z,10 Z,13 Z,16 Z)),3-hydroxyhexadecanoic acid and arachidonic acid could be the potential biomarkers for the QDBS group.CONCLUSION Three chest impediment syndromes have their own potential biomarkers.Each special metabolite has its owndifferent metabolic pathway.Both metabolismof cysteine and methionine,and metabolism of alanine,aspartate and glutamate are the main pathways in regulation of metabolic disorders in QSBS syndrome.Lysine biosynthesis and degradation,fatty acid metabolism,and glycerophospholipid metabolism are the main pathways in regulation of metabolic disorders in COQS syndrome.Arachidonic acid metabolism,fatty acid metabolism,fatty acid elongation in mitochondria,and vitamin B6 metabolism are the main pathways in regulation of metabolic disorders in QDBS syndrome.These endogenous substances were indicated as the special potential biomarkers for three chest impediment syndromes and worth studying in depth.

冠心病心血瘀阻证大鼠心肌组织代谢组学研究

目的研究冠心病心血瘀阻证大鼠心肌组织代谢产物谱,探讨其病证生物学基础。方法SD大鼠随机分为假手术组和模型组,采用冠状动脉左前降支结扎法制备冠心病心血瘀阻证大鼠模型,观察大鼠一般状态,检测舌象色度、心电图、心功能,HE染色、透射电镜观察心肌组织形态及超微结构,用超高效液相色谱-质谱技术检测心肌组织差异代谢物,并对代谢通路进行富集分析。结果与假手术组比较,模型组大鼠舌象色度R、G、B值均显著降低(P<0.05),心电图心率、ST段抬高幅度显著上升(P<0.05),左室射血分数、左室短轴缩短率显著下降(P<0.05),左室收缩末期内径、左室舒张末期内径显著上升(P<0.05);心肌组织结构模糊,有炎性细胞浸润,线粒体肿胀、破裂、溶解,嵴结构断裂减少。代谢组学共鉴定出29个假手术组与模型组差异显著的潜在生物标志物(7个上调、22个下调),主要富集于硫胺素代谢,精氨酸生物合成,嘌呤代谢,氨酰基-tRNA生物合成,丙氨酸、天冬氨酸和谷氨酸代谢,戊糖和葡萄糖醛酸相互转化,糖酵解/糖异生,缬氨酸、亮氨酸和异亮氨酸降解,三羧酸循环,丙酮酸代谢10条代谢通路。结论冠状动脉左前降支结扎法可较好地模拟冠心病心血瘀证病理过程,其病理机制涉及葡萄糖代谢、线粒体能量代谢、氨基酸代谢、蛋白质生物合成、嘌呤代谢等多层次代谢网络紊乱。

基于非靶向代谢组学的平菇子实体发育过程中菌丝体差异代谢物分析

为了解平菇生长发育过程中子实体形成的代谢物基础,采用超高效液相色谱-电喷雾串联四级杆质谱(UPLC-ESI-MS/MS)技术结合多变量统计分析方法对发菌完成期(MM)、原基期(MP)及子实体分化期(MF)的平菇菌丝体进行代谢组学分析。结果表明,主成分(PCA)模型分析结果显示3个时期平菇菌丝体中的代谢产物具有明显差异。通过正交偏最小二乘判别分析(OPLS‐DA),以VIP(varible importance in the projection)>1和差异倍数值(fold change)≥2或≤0.5为条件对MM vs MP、MM vs MF和MP vs MF中的差异代谢物进行比较分析,分别获得139个、147个和67个差异代谢物,变化倍数最大的物质包括氨基酸及其衍生物、脂质、生物碱、有机酸等,说明这些差异代谢物对平菇子实体发育具有重要影响。KEGG分析表明,苯丙氨酸代谢、色氨酸代谢、嘌呤代谢等20条代谢通路表现活跃。在子实体发育过程中,脂质、有机酸、核苷酸及其衍生物、氨基酸及其衍生物之间明显相关。以上研究结果为平菇子实体发育机制和标准化栽培提供了理论依据。

马钱子致大鼠体内毒性的研究——“装袋”算法和16S rRNA基因测序技术在毒理学研究中的应用

目的中药马钱子(Strychnos nux-vomica L.,SN)在临床上具有消肿止痛的功效,然而,由于含有生物碱类成分,马钱子具有一定毒性。人们对马钱子毒性所引起的大鼠内源性代谢变化及其对肠道微生物群代谢失调的潜在影响知之甚少,因此,马钱子的毒理学研究对其安全性评价具有重要意义。本研究将代谢组学和16S rRNA基因测序技术相结合来探索马钱子的致毒机制。方法通过急性、蓄积性和亚急性毒性试验,分别确定马钱子的中毒剂量、毒性强度和毒性靶器官。超高效液相色谱-质谱联用技术用于分析大鼠灌胃马钱子后的血清、肝脏和肾脏样本。利用基于装袋算法的决策树和K最近邻(K nearest neighbor,KNN)模型对组学数据进行分类。从大鼠粪便中提取样本后,使用高通量测序平台对细菌的16s rRNA V3-V4区域进行分析。结果装袋算法提高了样本分类的准确率。共鉴定出12个生物标志物,这些生物标志物的代谢失调可能是马钱子致体内毒性的原因。拟杆菌、粪厌氧棒菌、颤螺菌、双茎体菌等与肾肝功能的生理指标密切相关,这表明马钱子引起的肝肾损害可能与这些肠道细菌的代谢紊乱有关。结论本文揭示了马钱子的体内致毒机制,为马钱子临床上的安全合理使用提供了科学依据。

中医脾虚本质科学内涵研究之探讨

脾虚是中医理论体系的重要组成部分,其在不同的历史时期经历了起源、规范、成熟、完善、发展的过程。中医脾的生理功能涉及“脾主运化、升清、统血”;从脾本脏功能将“脾主运化”分解为“脾主运”和“脾主化”两部分进行研究,更有利于阐释脾主运化科学内涵。脾主运化是脾主升清的基础,脾主升清又是脾主运化的深化,脾主统血则是脾主升清的转归,三者存在递进的逻辑层次关系。随着蛋白质组学、代谢组学和肠道菌群研究的兴起,为脾虚的研究提供了技术支撑;另外,基于中医脾与内质网功能之间的关联性,从内质网应激角度探讨脾虚本质物质基础,为脾虚研究提供了新的方向。

基于代谢组学方法的红花治疗急性酒精性肝损伤的作用机制研究

红花在临床上对急性酒精性肝损伤(Acute Alcoholic Liver Injury,AALI)有很好的疗效,但治疗机制不甚明确。因此,阐明红花治疗AALI的分子作用机制对药物的进一步开发及应用具有十分重要的意义。实验以雄性Wistar大鼠为研究对象,模型组大鼠灌胃8 mL/kg的酒精以建立AALI模型,给药组大鼠以4.29 g/kg/天的剂量灌胃红花提取物。利用大鼠血清代谢组学分析方法鉴定与AALI相关的潜在生物标志物,并研究红花对这些生物标志物的调控机制。从苏木精和伊红(H&E)染色实验发现,灌胃后红花提取物减轻了肝细胞的损伤程度;与模型组相比,红花组中的丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)的表达水平降低,表明红花提取物具有肝保护作用。通过分析火山图,共鉴定出30种与AALI相关的生物标志物。在这些生物标志物中,红花可以对21个标志物产生回调效果。研究发现,红花可能通过对脂肪酸、磷脂、胆汁酸、氨基酸、核苷酸代谢的调控作用从而对AALI产生治疗效果。本文为红花的推广和临床应用提供了理论基础。

基于血清代谢组学探讨养筋解毒汤对糖尿病周围神经病变大鼠的作用机制

目的 基于血清代谢组学研究养筋解毒汤治疗糖尿病周围神经病变(Diabetic peripheral neuropathy,DPN)大鼠的作用机制。方法 将24只SPF级雄性SD大鼠按随机数字表法分为对照组、模型组、养筋解毒汤组,每组各8只,除对照组外,其余各组给予大鼠高脂高糖饲料饲喂8周,之后腹腔注射链脲佐菌制备DPN模型,采用体质量、体长、BMI指数和空腹GLU水平验证模型,模型成功后继续高脂高糖饲料饲喂8周后给予相应药物灌胃给药,2次/d,连续8周。采用空腹GLU水平评价疗效,采集大鼠血液分离血清利用非靶向代谢组学技术,通过主成分分析(PCA)、正交偏最小二乘法判别分析(OPLS-DA),结合t检验、变量重要性投影及差异倍数值筛选差异代谢物及可能的代谢通路。结果 经养筋解毒汤干预后与模型组比较,DPN大鼠血糖水平明显降低(P<0.01)。差异代谢物脯氨酸-亮氨酸(Pro-leu)、脯氨酸-异亮氨酸(Pro-Ile)、亮氨酸-酪氨酸(Leu-Tyr)等148种代谢物水平发生变化,同时对类固醇激素生物合成、精氨酸和脯氨酸代谢、甘氨酸、丝氨酸和苏氨酸代谢等代谢通路产生影响。结论 养筋解毒汤对DPN大鼠具有一定的治疗疗效,其机制可能与调节氨基酸及皮质激素代谢等有关。

长白猪和藏猪在不同日龄、种间的代谢物差异分析

通过对地方品种猪及外种猪的不同生长阶段代谢组学进行比较研究,以此了解地方品种猪与外种猪代谢组差异与耐粗饲性状的关系。采用UPLC-MS技术对7日龄和30日龄的长白猪和藏猪的粪便样品开展代谢组学研究,分析代谢物的变化情况,筛选差异代谢物的情况。结果显示,长白猪不同日龄代谢物VI P≥1的总共有99种,其中38种代谢物的比例是上升的,另61种代谢物主要存在下降趋势;藏猪不同日龄代谢物VIP≥1的总共有90种,其中31种代谢物的比例是上升的,另59种代谢物存在下降趋势;7日龄的长白猪和藏猪代谢物对比发现VIP≥1的总共有59种,其中29种代谢物的比例主要是上升趋势,另30种是下降趋势;30日龄的长白猪和藏猪代谢物对比VI P≥1的总共有66种,其中32种代谢物的比例是上升的,另34种代谢物存在下降趋势。说明不同种间、日龄代谢物含量存在差异,其中同种不同日龄猪的代谢物差异最多,说明随着年龄的增长猪对粗纤维等粗饲料的消化代谢能力有所差异。通过对代谢通路的分析显示,主要存在差异的代谢通路为Metabolic pathways、ABC transporters,参与差异代谢通路的代谢物主要是有机酸、核苷酸、氨基酸等相关代谢物,说明藏猪和长白猪在耐粗饲的特性上与粗饲料对肠道的影响有一定的关联性。此研究为解释在代谢组学方面藏猪耐粗饲特性提供了一定的理论基础。

从气血津液探析代谢组学在中医辨证中的应用

气血津液辨证是中医临床常用的辨证方法之一,是中医辨证论治诊疗体系的重要组成部分。在临床活动中,气血津液辨证因其辨证范围及主观因素的影响,具有一定的局限性。代谢组学可以从“微观辨证”的角度拓宽气血津液辨证的应用范围,提高临床诊断的准确率,提高中医辨证体系的科学性和客观性。为了实现中医证型的标准化,利用代谢组学技术对气血津液辨证进行研究具有一定的理论意义和实用价值。文章对近年来代谢组学在气血津液证型研究中的应用情况进行概述,以期为临床辨证提供新思路及新方法。

气滞胃痛颗粒治疗溃疡性结肠炎药效和机制研究

目的探讨气滞胃痛颗粒剂(qizhi weitong granule,QWG)治疗溃疡性结肠炎的药效及相关作用机制。方法建立2,4,6-三硝基苯磺酸诱导的溃疡性结肠炎(ulcerative colitis,UC)大鼠模型,通过考察结肠黏膜损伤评分(CMDI),结肠组织病理学变化以紧密连接蛋白Occludin和ZO-1的表达情况来评价QWG对UC大鼠的治疗作用。通过^(1)H-NMR代谢组学技术,以多元统计分析方法为手段,分析内源性代谢产物的动态变化,构建相关的代谢通路和代谢网络,探讨QWG治疗溃疡性结肠炎的可能的作用机制。结果QWG对结肠组织溃疡损伤有明显的修复作用,显著提高了大鼠结肠组织中Occludin和ZO-1蛋白的表达(P<0.01),共筛选鉴定出12个相关代谢生物标志物。结论QWG对溃疡性结肠炎有明显的保护作用,干预损伤的通路主要为甘氨酸、丝氨酸和苏氨酸代谢和三羧酸循环。

卵巢储备功能减退相关基因及组学研究进展

卵巢储备功能减退(DOR)是引起女性不孕症的常见原因之一。由于卵泡闭锁和排卵,随着年龄的增长,部分患者出现卵巢可募集的卵泡数目减少和受精能力减弱,以及同时伴有卵母细胞质量的下降和自然流产风险增高的现象。卵巢颗粒细胞(GCs)的程序性死亡可能导致了DOR卵巢中的大多数卵泡的最终闭锁,但是DOR女性生殖力低下的具体机制尚不明确,因此解析DOR的发病机制对于DOR的治疗和预防有着重要的指导意义。近年来对于DOR基因组学、代谢组学和蛋白质组学的研究取得了一定的进展,研究显示基因突变、脂类小分子和蛋白质分子的变化均与DOR的发生有关。本文就近年来在DOR基因组学、代谢组学和蛋白质组学中的研究进展作一综述,以期为早期诊断、干预和治疗DOR患者提供新思路。

基于代谢组学的中药治疗冠心病血瘀证生物标志物分析

目的基于代谢组学探讨中药(复方/单味)治疗不同物种冠心病血瘀证所筛选到的差异代谢物,总结中药干预冠心病血瘀证后的生物标志物及相关代谢通路。方法从中国知网、万方数据库、维普数据库、Embase、PubMed、the Cochrane Library、Web of Science数据库中检索中药(复方/单味)治疗冠心病血瘀证的代谢组学研究。对纳入研究的差异代谢物进行汇总,采用HMDB、PubChem-Subs、KEGG对代谢物进行分子注释,对代谢产物路径可视化采用metPA网络软件进行分析。结果共有8篇文献纳入本研究,计算两个物种中重复出现的代谢物后共统计89个差异代谢物主要参与了132条代谢路径。通过通路拓扑分析并对重复出现的代谢通路进行统计后选出了16条P值小于0.05的代谢通路作为中药(复方/单味)治疗不同物种冠心病血瘀证的代谢通路。对于富集于各条差异性代谢通路上的代谢物,在不同研究中重复筛选到的代谢物包括:苯丙氨酸,谷氨酰胺,甘氨酸,柠檬酸盐,胆碱,肌酸,乳酸,葡萄糖,花生四烯酸。结论各项研究中用于冠心病血瘀证治疗的中药(复方/单味)以血府逐瘀汤、桃红四物汤、养心通脉方、苏合香为代表。基于代谢组学的中药(复方/单味)治疗冠心病血瘀证的生物信息学分析显示其作用机制涉及糖代谢、氨基酸代谢、能量代谢、胆碱代谢、脂肪酸代谢等多个方面,基本的三羧酸循环参与其中。总结了包括乳酸、葡萄糖、柠檬酸、花生四烯酸、肌酸、苯丙氨酸、胆碱、谷氨酰胺以及甘氨酸在内的与冠心病血瘀证证候相关的差异代谢物。