生地黄凉血作用的肺脏代谢组学研究  

Lung metabonomics study on cooling blood effect of Rehmanniae Radix

作　　者：王永祥 周宁[1] 刘通 张金英[1] 郑晓珂[1,2] 冯卫生 WANG Yongxiang;ZHOU Ning;LIU Tong;ZHANG Jinying;ZHENG Xiaoke;FENG Weisheng(Henan University of Chinese Medicine,Zhengzhou 450046,China;Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan&Education Ministry of China,Zhengzhou 450046,China;Engineering Technology Research Center of Henan Traditional Chinese Medicine Development,Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学,郑州450046 [2]呼吸疾病中医药防治省部共建协同创新中心,郑州450046 [3]河南中医药大学河南省中药开发工程技术研究中心,郑州450046

出　　处：《中华中医药杂志》2023年第7期3296-3302,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家重点研发计划-中药现代化研究专项(No.2019YFC1708802);河南省高层次人才特殊支持计划“中原千人计划”-中原领军人才(No.ZYQR201810080);国家自然科学基金项目(No.81903805)。

摘　　要：目的:利用代谢组学研究血热证大鼠肺脏代谢的变化以及生地黄对其的干预作用。方法:采用“干酵母混悬液注射+无水乙醇灌胃”的复合造模法建立血热证大鼠模型;利用超高效液相串联四极杆飞行时间质谱(UHPLC-Q/TOF-MS)技术检测正常组、血热证模型组和生地黄组大鼠肺脏样本中内源性小分子代谢物,通过主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA)筛选出与血热证模型相关的生物标志物,并应用Mev软件对标志物的相对定量结果进行热度图绘制和聚类分析;结合MBRole、KEGG和MetaboAnalyst等在线数据库进行通路富集分析和代谢网络构建。结果:共鉴定出血热证相关生物标志物41个,富集得到3条显著受到干扰的代谢通路,包括精氨酸与脯氨酸代谢,丙氨酸、天冬氨酸和谷氨酸代谢,甘油磷脂代谢。结论:血热证大鼠肺脏内存在的能量代谢、氨基酸代谢、甘油磷脂代谢等多种代谢紊乱与肺细胞损伤、肺部炎症和气道损伤密切相关,经生地黄提取物干预后,血热证大鼠的上述肺部症状显著改善。Objective:Based on the metabonomic method,to study the changes of lung metabolism in rats with blood-heat syndrome and the intervention effect of Rehmanniae Radix on it.Methods:The blood-heat syndrome rat model was established by the compound modeling method of‘dry yeast suspension injection+absolute ethanol gavage’,and the lung samples of normal control group(NC),blood-heat syndrome model group(M)and Shengdihuang group(SD)were detected by UHPLC-Q/TOF-MS technology.The endogenous small molecule metabolites in lung samples were identified and screened for biomarkers related to the blood-heat syndrome model through principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA).Mev software was applied to perform heat map drawing and cluster analysis.Finally,integrate the information of MBRole,KEGG and MetaboAnalyst online databases for pathway enrichment analysis and metabolic network construction.Results:A total of 41 biomarkers related to blood-heat syndrome were identified,and three significantly interfered metabolic pathways were enriched,including metabolism of arginine and proline,metabolism of alanine,aspartic acid and glutamate,and glycerophospholipid metabolism.Conclusion:The metabolic disorders in lung tissue of blood-heat syndrome rats are closely related to lung cell injury,lung inflammation and airway injury.After the intervention of Rehmanniae Radix extract,all the above symptoms of the blood-heat syndrome rats improved significantly.

关 键 词：生地黄 血热证 肺组织 代谢组学 超高效液相串联四极杆飞行时间质谱 

分 类 号：R285.5[医药卫生—中药学]