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 Xuzhou 221004,China 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 Traditional Chinese Medicine and Western Medicine) Nanjing 210028,China.
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 Traditional Chinese Medicine and Western Medicine) Nanjing 210028,China.
Zhongguo Zhong Yao Za Zhi. 2019 May;44(10):2139-2148. doi: 10.19540/j.cnki.cjcmm.20190115.001.
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.
本文采用超高效液相色谱-飞行时间质谱联用技术（UPLC-Q-TOFMS），研究蒸制三七对N-乙酰苯肼（APH）诱导的溶血性贫血大鼠血浆内源性标志物的影响。旨在找出蒸制三七对溶血性贫血大鼠潜在的生物标志物及可能的补血机制。实验中，分别采用蒸制三七药对（蒸制三七-人参）和复方药物（三七养血胶囊）干预APH诱导的溶血性贫血模型大鼠，然后测定红细胞（RBC）、血红蛋白（Hb）等血常规指标及相关脏器指标。与空白组相比，模型组RBC和Hb水平显著降低（P<0.01），而肝、脾脏器指标升高（P<0.05）。血常规及脏器指标结果表明血虚模型成功建立。蒸制三七能显著提高大鼠RBC水平（P<0.01），各药物组相关指标有恢复至正常水平的趋势，验证了蒸制三七的补血作用。采用UPLC-Q-TOF-MS技术、主成分分析（PCA）和偏最小二乘判别分析（PLS-DA）分析正常组与模型组之间的代谢谱。在血浆中筛选出26个溶血性贫血潜在生物标志物。血虚大鼠血液中视黄醇、L-缬氨酸、花生四烯酸等9种代谢物下调，原卟啉Ⅸ、烟酰胺等17种代谢物上调。给大鼠灌胃蒸制三七、药对及复方制剂后，生物标志物的代谢水平可恢复至正常状态。推测蒸制三七可能通过改善缬氨酸、亮氨酸和异亮氨酸的生物合成以及视黄醇代谢、花生四烯酸代谢等代谢途径发挥补血作用。
