矿物药青礞石对慢性阻塞性肺疾病急性加重期(AECOPD)大鼠肺组织代谢组学研究  

Metabonomics research on lung tissue of rats with acute exacerbation of chronic obstructive pulmonary disease treated with mineral Chinese medicine Chloriti Lapis

作　　者：刘圣金 马瑜璐 房方 王瑞 杨文国 单晨啸 卞勇 严辉 张志杰[2] 奥·乌力吉[3] 段金廒 LIU Sheng-jin;MA Yu-lu;FANG Fang;WANG Rui;YANG Wen-guo;SHAN Chen-xiao;BIAN Yong;YAN Hui;ZHANG Zhi-jie;AO·Wuliji;DUAN Jin-ao(Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine,State Administration of Traditional Chinese Medicine Key Laboratory of Chinese Medicinal Resources Recycling Utilization y School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Inner Mongolia University for Nationalities,Tongliao 028000,China)

机构地区：[1]南京中医药大学药学院江苏省中药资源产业化过程协同创新中心中药资源产业化与方剂创新药物国家地方联合工程研究中心国家中医药管理局中药资源循环利用重点研究室,江苏南京210023 [2]中国中医科学院中药研究所,北京100700 [3]内蒙古民族大学,内蒙古通辽028000

出　　处：《中国中药杂志》2021年第12期3133-3143,共11页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81673566,81303178);全国矿物药资源普查项目(2019);江苏省研究生科研与实践创新计划项目(KYCX18-1608);2017年中医药公共卫生服务补助专项“全国中药资源普查项目”(财社[2017]66号)。

摘　　要：研究矿物药青礞石对慢性阻塞性肺疾病急性加重期(AECOPD)大鼠肺组织代谢物及代谢通路的干预情况。采用烟熏结合肺炎克雷伯菌感染的方法复制AECOPD痰热证大鼠模型。利用UPLC-Q-TOF-MS测定,通过SPSS 18.0、SIMCA 13.0等软件进行统计学处理,经文献查找以及在线数据库比对鉴定差异代谢物,分析可能的代谢通路。给药15 d对各组大鼠肺组织样品进行PLS-DA分析,结果显示各组大鼠肺组织代谢轮廓图均能很好的分离,说明青礞石和氨茶碱对AECOPD大鼠肺部代谢轮廓起到了显著的干预作用,且青礞石代谢轮廓与正常组更接近,干预效果优于氨茶碱。最终鉴定出15种潜在的差异代谢物:植物鞘氨醇(phytosphingosine)、二氢鞘氨醇(sphinganine)、十四酰肉碱(tetradecanoylcarnitine)、L-棕榈酰肉碱(L-palmitoylcarnitine)、反油肉碱(elaidic carnitine)、溶血卵磷脂lysoPC[18∶2(9Z,12Z)]、溶血卵磷脂lysoPC(16∶0)、溶血卵磷脂lysoPC[18∶1(9Z)]、溶血卵磷脂lysoPC(18∶0)、硬脂酸(stearic acid)、溶血卵磷脂lysoPC(15∶0)、花生四烯酸(arachidonic acid)、二十二碳五烯酸(docosapentaenoic acid)、亚油酸(linoleic acid)、棕榈酸(palmitic acid)。其中,青礞石能显著改善植物鞘氨醇、十四酰肉碱、L-棕榈酰肉碱、反油肉碱、lysoPC[18∶2(9Z,12Z)]、lysoPC(16∶0)、lysoPC[18∶1(9Z)]、硬脂酸、lysoPC(15∶0)、棕榈酸10种差异代谢物的水平(P<0.05),且干预效果优于氨茶碱。代谢通路分析显示,可能影响的代谢通路有8条,其中最为重要的代谢通路(pathway impact>0.1)有3条:亚油酸代谢(linoleic acid metabolism)、花生四烯酸代谢(arachidonic acid metabolism)和鞘脂类代谢(sphingolipid metabolism)。青礞石对AECOPD大鼠肺组织相关代谢物及代谢通路具有明显的干预作用,且作用优于氨茶碱。To study the effect of mineral Chloriti Lapis on pulmonary metabolites and metabolic pathways in lung tissues of rats with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).The AECOPD rat model of phlegm heat syndrome was replicated by the method of smoking combined with Klebsiella pneumoniae infection.Except for using UPLC-Q-TOF-MS analysis,SPSS 18.0,SIMCA 13.0 and other software were also used for statistical analysis.Through literature search and online database comparison,the differential metabolites were identified,and the possible metabolic pathways were analyzed.After 15 days of administration,PLS-DA analysis was carried out on lung tissue samples of rats in each group.The results showed that the metabolic profiles of lung tissues of rats in each group could be well separated,which indicated that Chloriti Lapis and aminophylline had significant intervention effect on the lung metabolic profile of rats with AECOPD.Moreover,the metabolic profile of Chloriti Lapis group was closer to that of control group,and the intervention effect was better than that of aminophylline group.As a result,15 potential differential metabolites were identified:phytosphingosine,sphinganine,tetradecanoylcarnitine,L-palmitoylcarnitine,elaidic carnitine,lysoPC[18∶2(9Z,12Z)],lysoPC(16∶0),lysoPC[18∶1(9Z)],lysoPC(18∶0),stearic acid,lysoPC(15∶0),arachidonic acid,docosapentaenoic acid,linoleic acid and palmitic acid.Among them,Chloriti Lapis could significantly improve the levels of 10 differential metabolites of phytosphingosine,tetradecanoylcarnitine,L-palmitoylcarnitine,elaidic carnitine,lysoPC[18∶2(9Z,12Z)],lysoPC(16∶0),lysoPC[18∶1(9Z)],stearic acid,lysoPC(15∶0),and palmitic acid(P<0.05).The intervention effect of Chloriti Lapis group was better than that of aminophylline group.Analysis of metabolic pathways showed that there were 8 possible metabolic pathways that could be affected,and three of the most important metabolic pathways(pathway impact>0.1)were involved:linoleic acid metabolism,arachido

关 键 词：矿物药 青礞石 慢性阻塞性肺疾病 肺组织 代谢组学 

分 类 号：R285.5[医药卫生—中药学]