基于高分辨率质谱的金欣口服液治疗小鼠RSV感染的血清脂质组学研究
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摘要
目的基于UHPLC-Q-Exactive Orbitrap MS高分辨率质谱,观察RSV诱发的肺炎模型小鼠的血清中脂质代谢的变化,分析金欣口服液对RSV肺炎小鼠中脂质代谢紊乱的调节作用,探讨金欣口服液治疗RSV诱发的病毒性肺炎的潜在机制。方法用RSV诱导小鼠病毒性肺炎,灌胃金欣口服液予以治疗,分别采集对照组、模型组、金欣口服液组小鼠的血清样本,提取脂质成分,采用LC-MS分析,采用主成分分析法(PCA)、聚类分析法(CA)等多元统计方法,对小鼠血清脂质代谢轮廓进行分析,同时进行Kruskal–Wallis test以及fold change法进行统计,寻找差异性脂质。结果 RSV感染导致小鼠肺部炎性细胞浸润及不同程度的肺炎,血清中多种脂质代谢物代谢紊乱,具体表现多数PC、PE出现明显上调,金欣口服液均能改善小鼠肺炎症状且显著恢复血清中异常紊乱的脂质。结论 RSV感染可导致小鼠血清中脂质代谢紊乱,而金欣口服液可一定程度恢复RSV模型中代谢紊乱的脂质,提示金欣口服液可通过调节脂质改善RSV诱发的肺炎。
OBJECTIVE Alipidomic method was applied to determine the lipidome in serum of mice based on high-resolution mass spectrometry(Q-Exactive Orbitrap).We investigated the changes of lipids in serum of mice with RSV to explore the regulation of Jinxin oral liquid on lipid metabolism caused by RSV.METHODS The serum samples from the blank group,the RSV model group and Jinxin oral liquid group mice were collected,and the lipids of these samples were extracted and further analyzed by high-resolution mass spectrometry.Multivariate statistical methods such as principal component analysis(PCA)and cluster analysis(CA)were used to analyze the lipid profiles,and the Kruskal-Wallis test and fold change were performed to find the differential lipids.RESULTS The lipids of serum between the blank control group and the RSV model group could be well distinguished,RSV infection in mice with metabolic abnormalities of lipids,the specific performance of the PC,PE was significantly upregulated,Jinxin oral liquid have a certain role in these lipids CONCLUSION RSV infection caused disturbances of lipid in vivo,and Jinxin oral liquid has a certain regulatory effect on the lipid metabolism disorder caused by RSV model.
OBJECTIVE Alipidomic method was applied to determine the lipidome in serum of mice based on high-resolution mass spectrometry(Q-Exactive Orbitrap).We investigated the changes of lipids in serum of mice with RSV to explore the regulation of Jinxin oral liquid on lipid metabolism caused by RSV.METHODS The serum samples from the blank group,the RSV model group and Jinxin oral liquid group mice were collected,and the lipids of these samples were extracted and further analyzed by high-resolution mass spectrometry.Multivariate statistical methods such as principal component analysis(PCA)and cluster analysis(CA)were used to analyze the lipid profiles,and the Kruskal-Wallis test and fold change were performed to find the differential lipids.RESULTS The lipids of serum between the blank control group and the RSV model group could be well distinguished,RSV infection in mice with metabolic abnormalities of lipids,the specific performance of the PC,PE was significantly upregulated,Jinxin oral liquid have a certain role in these lipids CONCLUSION RSV infection caused disturbances of lipid in vivo,and Jinxin oral liquid has a certain regulatory effect on the lipid metabolism disorder caused by RSV model.
引文
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[11]李佳曦,汪受传,徐建亚,等.金欣口服液含药血清及其有效单体白藜芦醇对RSV的RNA聚合酶转录活性的影响[J].南京中医药大学学报,2011,27(1):36-39.
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[18]HITE RD,SEEDS MC,JACINTO RB,et al.Lysophospholipid and fatty acid inhibition of pulmonary surfactant:non-enzymatic models of phospholipase A2surfactant hydrolysis.[J].BBA-Biomembranes,2005,1720(1):14-21.
[19]杜丽娜,单进军,谢彤,等.基于液相质谱联用的黄芩水提液抗病毒效应的脂质组学研究[J].中华中医药杂志,2015,30(5):1728-1733.
[20]陈华,于海洲,彭创业.HPLC-ELSD法同时测定丙泊酚注射液中溶血磷脂酰胆碱和溶血磷脂酰乙醇胺的含量[J].药物分析杂志,2014,34(3):442-446.
[21]林丽丽,谢彤,汪受传,等.代谢组学在儿科疾病中的应用[J].南京中医药大学学报,2017,33(2):182-186.
[22]ENHORNING G.Surfactant in airway disease[J].Chest,2008,133(4):975-980.
[2]GROVES HT,CUTHBERTSON L,JAMES P,et al.Respiratory disease following viral lung infection alters the murine gut microbiota[J].Front Immunol,2018,9:182.
[3]孟欣,单进军,谢彤,等.基于血浆代谢组学分析金欣口服液治疗小鼠RSV肺炎的作用机制[J].中国实验方剂学杂志,2016,22(17):71-76.
[4]MARI N,YOJI N,MOORE ML,et al.Phosphatidylglycerol provides short-term prophylaxis against respiratory syncytial virus infection[J].J Lipid Res,2013,54(8):2133.
[5]杜丽娜,单进军,徐建亚,等.金欣口服液不同化学部位对呼吸道合胞病毒感染的影响[J].南京中医药大学学报,2013,29(2):165-168.
[6]SHEN CS,ZHANG ZG,XIE T,et al.Jinxin oral liquid inhibits human respiratory syncytial virus-induced excessive inflammation associated with blockade of the NLRP3/ASC/Caspase-1pathway[J].Biomed Pharmacother,2018,103:1376.
[7]彭琳秀,陈良慧,狄留庆,等.基于UPLC/LTQ-Orbitrap-MS技术的复方祖师麻片抗类风湿关节炎的血浆代谢组学研究[J].中草药,2017,48(10):1964-1970.
[8]FESSLER MB,SUMMER RS.Surfactant lipids at the host-environment interface:Metabolic sensors,suppressors,and effectors of inflammatory lung disease[J].Am J Respir Cell Mol Biol,2016,54(5):624-635.
[9]钱文娟,杨瑞,谢彤,等.蒲地蓝消炎口服液治疗甲型H1N1流感病毒性肺炎的GC-MS代谢组学研究[J].中草药,2018,49(10):2258-2264.
[10]漆欣,李菊莲,王银平,等.脂质代谢组学在针灸研究中的应用展望[J].中医药导报,2018,23(14):93-95,104.
[11]李佳曦,汪受传,徐建亚,等.金欣口服液含药血清及其有效单体白藜芦醇对RSV的RNA聚合酶转录活性的影响[J].南京中医药大学学报,2011,27(1):36-39.
[12]陈争光,汪受传,徐建亚,等.金欣口服液对RSV感染BALB/c小鼠TLR3信号转导通路负调控因子SOCS1表达的调控作用[J].中国中西医结合杂志,2014,34(12):1499-1506.
[13]TSUGAWA H,CAJKA T,KIND T,et al.MS-DIAL:dataindependent MS/MS deconvolution for comprehensive metabolome analysis[J].Nature methods,2015,12(6):523-526.
[14]DEFELICE BC,MEHTA SS,SAMRA S,et al.Mass spectral feature list optimizer(MS-FLO):a tool to minimize false positive peak reports in untargeted liquid chromatography-mass spectroscopy(LC-MS)data processing[J].Analyt Chem,2017,89(6):3250-3255.
[15]NUMATA M,CHU HW,DAKHAMA A,et al.Pulmonary surfactantphosphatidylglycerol inhibits respiratory syncytial virus-induced inflammation and infection.[J].Proc Natl Acad Sci USA,2010,107(1):320-325.
[16]BARREIRA ER,PRECIOSO AR,BOUSSO A.Pulmonary surfactant in respiratory syncytial virus bronchiolitis:The role in pathogenesis and clinical implications[J].Pediatr Pulmonol,2011,46(5):6.
[17]谢露,尹晓娟.新生儿肺表面活性物质研究新进展[J].中国儿童保健杂志,2012,20(3):235-237.
[18]HITE RD,SEEDS MC,JACINTO RB,et al.Lysophospholipid and fatty acid inhibition of pulmonary surfactant:non-enzymatic models of phospholipase A2surfactant hydrolysis.[J].BBA-Biomembranes,2005,1720(1):14-21.
[19]杜丽娜,单进军,谢彤,等.基于液相质谱联用的黄芩水提液抗病毒效应的脂质组学研究[J].中华中医药杂志,2015,30(5):1728-1733.
[20]陈华,于海洲,彭创业.HPLC-ELSD法同时测定丙泊酚注射液中溶血磷脂酰胆碱和溶血磷脂酰乙醇胺的含量[J].药物分析杂志,2014,34(3):442-446.
[21]林丽丽,谢彤,汪受传,等.代谢组学在儿科疾病中的应用[J].南京中医药大学学报,2017,33(2):182-186.
[22]ENHORNING G.Surfactant in airway disease[J].Chest,2008,133(4):975-980.