基于代谢组学技术探究藏药蕨麻对环磷酰胺致骨髓抑制的改善作用机制  

Exploring the protective mechanism of Tibetan medicine Potentilla anserine on cyclophosphamide-induced myelosuppression based on metabonomics technology

作　　者：刘静贤 罗晓敏 顾健 黄时光 王琴 刘伟 龚普阳 LIU Jing-xian;LUO Xiao-min;GU Jian;HUANG Shi-guang;WANG Qin;LIU Wei;GONG Pu-yang(College of Pharmacy,Southwest Minzu University,Chengdu 610041,China)

机构地区：[1]西南民族大学药学院,四川成都610041

出　　处：《药学学报》2023年第7期1851-1858,共8页Acta Pharmaceutica Sinica

基　　金：西南民族大学中央高校基本科研业务费(2020NQN38);西南民族大学大学生创新创业训练计划项目(202210656042).

摘　　要：探究蕨麻水提物对环磷酰胺诱导骨髓抑制小鼠的影响及其代谢组学机制。采用环磷酰胺建立骨髓抑制小鼠模型并给予蕨麻水提物治疗,计算各组小鼠胸腺与脾指数,检测血常规变化,测定骨髓有核细胞数,并采用苏木精-伊红(hematoxylin-eosin,HE)染色进行骨髓病理学分析。测定小鼠血清中白细胞介素3(interleukin 3,IL-3)、白细胞介素6(interleukin 6,IL-6)、促红细胞生成素(erythropoietin,EPO)、粒细胞巨噬细胞集落刺激因子(granulocyte macrophagecolonystimulatingfactor,GM-CSF)、丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)及过氧化氢酶(catalase,CAT)水平。借助UPLC-Q-TOF/MS进行血清非靶向代谢组学分析,探析生物标志物变化及所涉及的代谢通路。动物实验操作遵循西南民族大学实验动物伦理委员会规定。蕨麻高剂量组可显著改善环磷酰胺诱导的小鼠外周血中白细胞(white blood cell,WBC)、红细胞(red blood cell,RBC)计数及血红蛋白(hemoglobin,HGB)水平下降(P<0.05),显著增加股骨骨髓中有核细胞数目及造血组织面积。蕨麻中、高剂量可显著改善小鼠血清中SOD、CAT、MDA、IL-6及GM-CSF水平(P<0.05),对IL-3及EPO表达无显著影响(P>0.05)。血清代谢组学分析表明蕨麻水提物可通过调控缬氨酸、亮氨酸、L-天冬酰胺及羟基异己酸等13个差异代谢物介导的氨酰基-tRNA生物合成、缬氨酸、亮氨酸和异亮氨酸的生物合成等通路改善骨髓抑制。蕨麻可改善环磷酰胺诱导的小鼠骨髓造血功能抑制,其作用机制可能与抗氧化、促进造血相关细胞因子的表达及调节相关代谢通路有关。The study aims to explore the effects and mechanisms of water extract of Potentilla anserina(PA)on myelosuppression mice induced by cyclophosphamide based on metabonomics.The myelosuppressive mouse model was established by injected with cyclophosphamide and treated with water extract of PA.Thymus and spleen indexes,peripheral hemogram and bone marrow nucleated cells of each group was detected.Bone marrow pathology analysis was performed by hematoxylin-eosin staining.The levels of interleukin 3(IL-3),interleukin 6(IL-6),erythropoietin(EPO),granulocyte colony stimulating factor(GM-CSF),malondialdehyde(MDA),superoxide dismutase(SOD)and catalase(CAT)in serum were measured.The changes of biomarkers and related metabolic pathways were analyzed by UPLC-Q-TOF/MS-based metabonomics.Animal experiments were approved by the Animal Ethics Committee of Southwest Minzu University.The high doses of PA could significantly improve the decrease of white blood cell(WBC),red blood cell(RBC)counts and hemoglobin(HGB)levels of mice induced by cyclophosphamide(P<0.05),and significantly increase the number of nucleated cells and the area of hematopoietic tissue in femoral bone marrow.The medium and high doses of PA could significantly improve the serum levels of SOD,CAT,MDA,IL-6 and GM-CSF(P<0.05),and have no significant effect on the expression of IL-3 and EPO(P>0.05).Serum metabolomics analysis showed that the aqueous extracts of PA could alleviate myrosuppression by regulating the aminoacyl-tRNA,valine,leucine and isoleucine biosynthesis mediated by 13 different metabolites such as valine,leucine,asparagine and hydroxyisohexic acid.PA improve the inhibition of hematopoietic function in myelosuppression mouse,and its mechanisms may be related to anti-oxidation and promoting the expression of hematopoietic-related cytokines and regulating the related metabolic pathways.

关 键 词：蕨麻 环磷酰胺 骨髓抑制 代谢组学 

分 类 号：R917[医药卫生—药物分析学]