基于UPLC/LTQ-Orbitrap-MS技术对去卵巢大鼠的脂质组学研究
作者:
作者单位:

(南京中医药大学附属医院 江苏省中医院妇科, 江苏省南京市 210029)

作者简介:

何若晗,硕士研究生,研究方向为绝经综合征的基础与临床,E-mail为592222057@qq.com。通信作者卢苏,主任中医师,教授,博士研究生导师,研究方向为绝经综合征的基础和临床,E-mail为lusu0926@sina.com。

基金项目:

国家自然科学基金资助项目(81574009);江苏省自然科学基金资助项目(BK20151600);江苏省卫生计生委科研课题资助项目(Q201602)


Lipidomics study of ovariectomized rats based on UPLC/LTQ-Orbitrap-MS technology
Author:
Affiliation:

Department of Gynaecology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Jiangsu, Nanjing 210029, China)

  • 摘要
  • | |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • | |
    摘要:

    目的 分析绝经期大鼠脂代谢物的变化,进而识别代谢变化中潜在的生物标志物。方法 将4月龄雌性SD大鼠随机分为假手术(Sham)组和去卵巢(OVX)组。采用UPLC/TQ-O rbitrap-MS的代谢组学分析方法,用主成分分析法(PCA)以及正交-偏最小二乘法分析法(OPLS-DA)进行多元统计分析,筛选与疾病有关的潜在生物标记物。结果 通过OPLS-DA得分图能够将假手术组和去卵巢组的大鼠血浆脂质代谢物很好地聚类区分,两组之间无明显的交叉重叠。与假手术组相比,去卵巢组中神经酰胺(Cer)、鞘磷脂(SM)、血小板活化因子(PAF)、溶血磷脂酰胆碱(LPC)、甘油三酯(TG)、ω-6不饱和脂肪酸(ω-6PUFA)的相对含量上升;甘油二酯(DG)、磷脂酰丝氨酸(PS)和磷脂酰甘油(PG)的相对含量下降。两组共测得35种内源性代谢产物,其中Cer、SM、PAF、LPC、TG、DG、PS、PG、ω-6PUFA等9种为潜在的生物标记物。结论 筛选出的9种潜在标志物均与绝经综合征有关,为老年性退化性疾病生物标志物的早期发现奠定基础。

    Abstract:

    Aim To analyze the changes of lipid metabolites in menopausal rats and identify potential biomarkers in metabolic changes. Methods 4-month-old female SD rats were randomly divided into sham operation (Sham) group and ovariectomized (OVX) group. Using UPLC/LTQ-Orbitrap-MS metabonomics analysis method, principal component analysis (PCA) and orthogonal-partial least squares analysis (OPLS-DA) were used for multivariate statistical analysis to screen potential biomarkers related to diseases. Results The OPLS-DA score plot could be used to distinguish the plasma lipid metabolites of rats in the sham group and ovariectomized group, and there was no significant overlap between the two groups. Compared with the sham group, the relative contents of ceramide (Cer), sphingomyelin (SM), platelet activating factor (PAF), lysophosphatidylcholine (LPC), triglyceride (TG) and omega-6 unsaturated fatty acid (ω-6PUFA) increased in the ovariectomized group, while the relative contents of diglyceride (DG), phosphatidylglycerin (PG) and phosphatidylserine (PS) decreased. A total of 35 endogenous metabolites were detected in both groups, including Cer, SM, PAF, LPC, TG, DG, PS, PG, ω-6PUFA as potential biomarkers. Conclusion All the 9 potential biomarkers were related to menopausal syndrome, which laid a foundation for the early detection of biomarkers of senile degenerative diseases.

    参考文献
    [1] Wishart DS.Current progress in computational metabolomics.Brief Bioinform, 7,8(5):279-293.
    [2] Han X, Gross RW.Global analyses of cellular lipidomes directly from crude extracts of biological samples by ESI mass spectrometry:a bridge to lipidomics.J Lipid Res, 3,4(6):1071-1079.
    [3] Oresic M.Metabolomics, a novel tool for studies of nutrition, metabolism and lipid dysfunction.Nutr Metab Cardiovasc Dis, 9,9(11):816-824.
    [4] Hu T, Zhang JL.Mass-spectrometry-based lipidomics.J Sep Sci, 8,1(1):351-372.
    [5] Alewijnse AE, Peters SL.Sphingolipid signalling in the cardiovascular system:good, bad or both?.Eur J Pharmacol, 8,5(2-3):292-302.
    [6] Nilsson A,Duan RD.Absorption and lipoprotein transport of sphingomyelin.J Lipid Res, 6,7(1):154-171.
    [7] 王尹曼, 陈学颖, 徐磊, 等.鞘磷脂与冠状动脉粥样硬化性心脏病患者冠状动脉狭窄程度的相关性研究.中国临床医学, 5,2(03):310-3,7.
    [8] 李剑军, 陈佩芳, 吴满平, 等.磷脂对高密度脂蛋白3介导大鼠腹腔巨噬细胞内胆固醇流出的影响.中国动脉硬化杂志, 0,8(2):107-110.
    [9] Castro BM, Prieto M, Silva LC.Ceramide:a simple sphingolipid with unique biophysi -cal properties.Prog Lipid Res, 4,4:53-67.
    [10] Li H, Junk P,Huwiler A, et al.Dual effect of ceramide on human endothelial cells:induction of oxidative stress and transcriptional upregulation of endothelial nitric oxide synthase.Circulation, 2,6(17):2250-2256.
    [11] Ramírez S, Martins L, Jacas J, et al.Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin.Diabetes, 3,2(7):2329-2337.
    [12] Nomikos T, Fragopoulou E, Antonopoulou S, et al.Mediterranean diet and platelet -activating factor:a systematic review.Clin Biochem, 8,0:1-10.
    [13] 刘本君, 郭宏军, 葛佳瑞, 等.多不饱和脂肪酸与肿瘤关系的研究进展.畜牧兽医科技信息, 2007, (5):7-8.
    [14] Schmitz G, Ruebsaamen K.Metabolism and atherogenic diseaseassociation of lysophosphatidylcholine.Atherosclerosis, 0,8(1):10-18.
    [15] Tsai TY, Leong IL, Cheng KS, et al.Lysophosphatidylcholine-induced cytotoxicity and protection by heparin in mouse brain bEND.3 endothelial cells.Fundam Clin Pharmacol, 2019, 33(1): 52-62.
    [16] Domeij H, Hua X, Su J, et al.Annexin A5 inhibits atherogenic and pro-inflammatory effects of lysophosphatidylcholine.Prostaglandins Other Lipid Mediat, 3,6:72-78.
    [17] 刘勇, 余艳荣, 彭维杰, 等.吴茱萸次碱改善溶血性磷脂酰胆碱诱导的内皮细胞缝隙连接细胞间通讯功能障碍.中国药理学通报, 3,9(11):1514-1519.
    [18] Rikitake Y, Kawashima S, Yamashita T, et al.Lysophosphatidylcholine inhibits endothelial cell migration and proliferation via inhibition of the extracellular signal-regulated kinase pathway.Arterioscler Thromb Vasc Biol, 0,0(4):1006-1012.
    [19] 亢爱春, 霍勇, 齐丽彤.溶血磷脂酰胆碱在动脉粥样硬化中的作用.中国动脉硬化杂志, 6,4(12):1083-1086.
    [20] Palmisano BT, Zhu L, Eckel RH, et al.Sex differences in lipid and lipoprotein metabolism.Mol Metab, 8,5:45-55.
    [21] Zhang X,Qi R, Xian X, et al.Spontaneous atherosclerosis in aged lipoprotein lipase-deficient mice with severe hypertriglyceridemia on a normal chow diet.Circ Res, 8,2(2):250-256.
    [22] 韩贻仁.分子细胞生物学.第4版.北京:科学出版社, 2012:257-258.
    [23] Maki KC, Davidson MH, Tsushima R, et al.Consumption of diacylglycerol oil as part of a reduced-energy diet enhances loss of body weight and fat in comparison with consumption of a triacylglycerol control oil.Am J Clin Nutr, 2,6(6):1230-1236.
    [24] Pang LQ, Liang QL, Wang YM, et al.Simultaneous determination and quantification of seven majorphospholipid classes in human blood using normal-phase liquid chromatography coupled with electrospray mass spectrometry and the application in diabetesnephropathy.J Chromatogr B Analyt Technol Biomed Life Sci, 8,9(1-2):118-125.
    相似文献
    引证文献
引用本文

何若晗,陈赟,卢苏.基于UPLC/LTQ-Orbitrap-MS技术对去卵巢大鼠的脂质组学研究[J].中国动脉硬化杂志,2019,27(4):323~329.

复制
分享
文章指标
  • 点击次数:738
  • 下载次数: 736
历史
  • 收稿日期:2018-10-15
  • 最后修改日期:2019-01-11
  • 在线发布日期: 2019-04-08