中国中药杂志

2019, v.44(10) 2139-2148

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基于代谢组学研究熟三七发挥补血作用的机制
Study on blood enrichment mechanism of steamed notoginseng based on metabolomics method

张银;费倩倩;汪晶;朱粉霞;陈彦;汤道权;陈斌;
ZHANG Yin;FEI Qian-qian;WANG Jing;ZHU Fen-xia;CHEN Yan;TANG Dao-quan;CHEN Bin;Jiangsu Provincial Key Laboratory for New Drug Research and Clinical Pharmacy,Xuzhou Medical University;Key Laboratory for Traditional Chinese Medicine Drug Release System Under State Administration of Traditional Chinese Medicine,Jiangsu Province Academy of Traditional Chinese Medicine,the Third Clinical Medical College of Nanjing University of Chinese Medicine ( Affiliated Provincial Hospital of Integrated Traditiona

摘要(Abstract):

该文运用高效液相色谱-飞行时间质谱联用(UPLC-Q-TOF-MS)技术研究熟三七(蒸制三七)对乙酰苯肼(APH)致溶血性贫血大鼠血浆中内源性标志物的影响,旨在发现熟三七对溶血性贫血大鼠补血作用的潜在生物标记物及可能的补血作用机制。采用熟三七、药对(熟三七-人参)和复方(三七养血胶囊)分别干预APH诱导的溶血性贫血模型大鼠,测定红细胞(RBC)、血红蛋白(Hb)等血液常规指标以及相关脏器指标。与空白组比较,模型组大鼠RBC,Hb水平显著降低(P<0. 01),肝、脾脏器指数升高(P<0. 05),血常规和脏器指标测定结果表明血虚证大鼠造模成功。而熟三七能显著升高大鼠RBC水平(P<0. 01),各给药组的相关指标均有良好的回调趋势,验证了熟三七的补血作用。对收集的血浆样品应用UPLC-Q-TOF-MS技术,并结合主成分分析(PCA)和偏最小二乘法-判别分析(PLS-DA),对正常组、模型组之间的代谢谱进行分析,筛选出26个溶血性贫血的潜在生物标记物。血虚大鼠体内视黄醇、L-缬氨酸、花生四烯酸等9个代谢物下调,原卟啉Ⅸ、烟酰胺等17个代谢物上调。大鼠给予熟三七、药对、复方后可使生物标志物代谢水平向正常状态转归,推测熟三七可能从改善缬氨酸、亮氨酸和异亮氨酸的生物合成、视黄醇代谢、花生四烯酸代谢等8条代谢途径发挥补血的作用。
In this paper,ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOFMS) technique was used to study the effects of steamed notoginseng on endogenous markers in plasma of rats with hemolytic anemia induced by N-acetyl phenyl hydrazine( APH). The aim was to find out the potential biomarkers and possible blood enriching mechanism of steamed notoginseng on hemolytic anemia rats. In the experiment,steamed notoginseng medicine pair( steamed notoginseng-ginseng)and compound medicines( Sanqi Yangxue Capsules) were used respectively to intervene in APH-induced hemolytic anemia model rats.Then blood routine indexes such as red blood cells( RBC),hemoglobin( Hb) and related organ indexes were determined. As compared with the blank group,the RBC and Hb levels in the model group were substantially decreased( P< 0. 01),while the liver and spleen organ indexes were increased( P< 0. 05). The results of blood routine and organ index demonstrated that the blood deficiency model was successfully established. Steamed notoginseng can significantly increase the RBC level of rats( P<0. 01),and the related indicators of each drug group had a trend of returning to normal levels,verifying the blood enriching effect of steamed notoginseng. The UPLC-Q-TOF-MS technique,principal component analysis( PCA) and partial least squares-discrimination analysis( PLS-DA) were used to analyze the metabolic profiles between the normal group and the model group. Twenty-six potential biomarkers for hemolytic anemia were screened in plasma. Nine metabolites such as retinol,L-valine,and arachidonic acid were down-regulated in the blood deficiency rats,and 17 metabolites such as protoporphyrin Ⅸ and niacinamide were up-regulated. The metabolic level of biomarkers could be changed to a normal state after rats were given with steamed notoginseng,drug pairs,and compound prescriptions. It can be speculated that steamed notoginseng may play a role of blood tonifying by improving biosynthesis of valine,leucine and isoleucine,as well as metabolic pathways such as retinol metabolism and arachidonic acid metabolism.

关键词(KeyWords): 熟三七;血虚;代谢组学
steamed notoginseng;blood deficiency;metabolomics

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81102812);; 江苏省新药研究与临床药学重点实验室开放研究课题项目(KF-XY201506)

作者(Authors): 张银;费倩倩;汪晶;朱粉霞;陈彦;汤道权;陈斌;
ZHANG Yin;FEI Qian-qian;WANG Jing;ZHU Fen-xia;CHEN Yan;TANG Dao-quan;CHEN Bin;Jiangsu Provincial Key Laboratory for New Drug Research and Clinical Pharmacy,Xuzhou Medical University;Key Laboratory for Traditional Chinese Medicine Drug Release System Under State Administration of Traditional Chinese Medicine,Jiangsu Province Academy of Traditional Chinese Medicine,the Third Clinical Medical College of Nanjing University of Chinese Medicine ( Affiliated Provincial Hospital of Integrated Traditiona

DOI: 10.19540/j.cnki.cjcmm.20190115.001

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