Page 49 - 2021年17期

黄芪注射液中次生成分作用于白细胞减少症模型小鼠的代谢组

学研究 Δ

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曲婷丽 ，刘 腾 ，郑 茜 ，卢晓林 ，赵正保 ，李震宇（1.山西医科大学药学院，太原 030001；2.山西大学中
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医药现代研究中心，太原 030006）
中图分类号 R285.5 文献标志码 A 文章编号 1001-0408（2021）17-2091-06
DOI 10.6039/j.issn.1001-0408.2021.17.08
摘 要 目的：研究黄芪注射液中次生成分作用于白细胞减少症模型小鼠的代谢组学。方法：将小鼠分为正常组、模型组、黄芪注
射液组（0.004 mL/g）及其次生成分低、中、高剂量组（0.004、0.008、0.016 mL/g），每组7只。除正常组外，其余各组小鼠均腹腔注射
环磷酰胺（80 mg/kg）以复制白细胞减少症模型。造模成功后，各给药组小鼠腹腔注射相应药物，正常组和模型组小鼠腹腔注射等
体积无菌注射用水，每天1次，连续7 d。实验期间，每隔2 d测定小鼠的体质量变化。末次给药后，采用动物血液分析仪检测小鼠
的血常规指标[白细胞（WBC）、中性粒细胞（NE）、淋巴细胞（LY）、单核细胞（MO）计数]，采用超高效液相色谱-四极杆/静电场轨道
阱高分辨质谱法，结合多元统计分析方法，对小鼠血清进行代谢组学分析。结果：与模型组比较，次生成分低剂量组小鼠体质量在
给药第4、8天时均显著增加（P＜0.05），次生成分各剂量组小鼠血清中WBC、NE、LY、MO计数均显著升高（P＜0.05或P＜0.01）。
经代谢组学分析显示，黄芪注射液中次生成分可显著回调白细胞减少症模型小鼠血清中亚精胺、尿酸、柠檬酸、烟酰胺、二十碳五
烯酸、亚油酸、芥酰胺、1-磷酸鞘氨醇等8个差异代谢物的含量，其作用涉及亚油酸代谢途径、烟酸和烟酰胺代谢途径、三羧酸循环
途径。结论：黄芪注射液中次生成分具有升高白细胞减少症模型小鼠白细胞的作用，其作用机制可能与干预亚油酸代谢途径、烟
酸和烟酰胺代谢途径、三羧酸循环途径有关。
关键词 黄芪注射液；次生成分；代谢组学；白细胞减少症
Metabonomics Study on the Effects of Secondary Components of Astragalus membranaceus Injection on
Leukopenia Model Mice
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QU Tingli ，LIU Teng ，ZHENG Qian ，LU Xiaolin ，ZHAO Zhengbao ，LI Zhenyu（1. School of Pharmacy，
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Shanxi Medical University，Taiyuan 030001，China；2. Modern Research Center of TCM，Shanxi University，
Taiyuan 030006，China）
ABSTRACT OBJECTIVE： To study metabonomics of secondary components of Astragalus membranaceus injection on
leukopenia model mice. METHODS：The mice were divided into normal group，model group，A. membranaceus injection group
（0.004 mL/g），secondary components low-dose，medium-dose and high-dose groups（0.004，0.008，0.016 mL/g），with 7 mice in
each group. Except for normal group， other groups were given cyclophosphamide （80 mg/kg） intraperitoneally to induce
leukopenia model. After modeling，administration groups were given relevant medicine intraperitoneally，and normal group and
model group were given constant volume of sterile water for injection intraperitoneally，once a day，for consecutive 7 days. During
the experiment，the changes of body weight of mice were measured every 2 days. After the last administration，the blood routine
indexes [white blood cell（WBC），neutrophil（NE），lymphocyte（LY）and monocyte（MO）counts] of mice were detected by
animal blood analyzer. UPLC-Q Exactive Orbitrap-HRMS combined with multivariate statistical analysis were used to analyze the
metabonomics of mice serum. RESULTS：Compared with model group，body weight of mice in the secondary component low-dose
group increased significantly on the 4th and 8th day of administration（P＜0.05），and the counts of WBC，NE，LY and MO in
serum of mice in secondary component groups increased significantly（P＜0.05 or P＜0.01）. Metabonomic analysis showed that the
secondary components of A. membranaceus injection could significantly regulate the contents of 8 endogenous metabolites in
serum， including spermidine， uric acid， citric acid， nicotinamide， eicosapentaenoic acid， linoleic acid， erucamide and
sphingosine-1-phosphate. Their effects involved linoleic acid metabolism pathway，nicotinic acid and nicotinamide metabolism
pathway and tricarboxylic acid cycle pathway. CONCLUSIONS：The secondary components of A. membranaceus injection possess
the effect of increasing white blood cells in leukopenia model mice，the mechanism of which may be related to intervention of
linoleic acid metabolism pathway， nicotinic acid and
Δ 基金项目：山西省回国留学人员科研资助项目（No.2017-017）
nicotinamide metabolism pathway，and tricarboxylic acid cycle
＊副教授，硕士生导师，博士。研究方向：中药药效物质及代谢组
学。电话：0351-3985290。E-mail：qutingli@126.com pathway.
# 通信作者：教授，硕士生导师，博士。研究方向：中药新药及 KEYWORDS Astragalus membranaceus injection；
代谢组学。电话：0351-3985290。E-mail：zhengbao_z@163.com Secondary components；Metabolomics；Leukopenia

中国药房 2021年第32卷第17期 China Pharmacy 2021 Vol. 32 No. 17 ·2091 ·