基于血清1H-NMR代谢组学的地榆升白片治疗白细胞减少症作用机制研究  

Mechanism of Diyu Shengbai Tablets Treating Leukopenia Based on Serum 1H-NMR Metabolomics

作　　者：刘鹏 田俊生[2] Liu Peng;Tian Junsheng(Shanxi Pharmaceutical Vocational College,Taiyuan 030031;Modem Research Center for Traditional Chinese Medicine,Shanxi University,Taiyuan 030006)

机构地区：[1]山西药科职业学院,太原030001 [2]山西大学中医药现代研究中心,太原030006

出　　处：《中药药理与临床》2020年第3期193-198,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：中国博士后科学基金面上资助项目(编号:2016M602414)。

摘　　要：目的:明确地榆升白片治疗白细胞减少症的药理作用,并采用核磁(~1H-NMR)代谢组学的方法探讨其对内源性代谢物的调节作用,阐释其作用机制。方法:构建4T1乳腺癌荷瘤小鼠,采用腹腔注射80 mg/kg环磷酰胺进行造模,建立肿瘤化疗后白细胞减少症模型。将小鼠随机分为正常对照组、模型对照组和地榆升白片0.14 g/kg组,连续灌胃给药一周。利用传统药效学指标(血常规和脏器指数)评价地榆升白片药效。采用~1H-NMR技术对血清样本进行分析,寻找与地榆升白片疗效相关的差异代谢物,并对其关键代谢通路进行分析,阐释其作用机制。结果:与正常对照组比较,模型对照组小鼠白细胞含量显著降低(P<0.01),脾脏和胸腺指数显著下降(P<0.01),肝脏指数明显升高(P<0.05)。与模型对照组相比,地榆升白片0.14 g/kg组可显著升高白细胞的含量(P<0.01),并明显改善脏器指数(P<0.05或P<0.01)。代谢组学结果表明地榆升白片可明显回调8种差异代谢物的水平(P<0.05或P<0.01),并通过调节谷氨酰胺和谷氨酸代谢、氮代谢、精氨酸生物合成、丙氨酸,天冬氨酸和谷氨酸代谢等代谢途径发挥作用。结论:地榆升白片改善白细胞减少症的主要效应机制与调节谷氨酰胺和谷氨酸代谢、氮代谢、精氨酸生物合成、丙氨酸,天冬氨酸和谷氨酸代谢等有关。Objective:To study the pharmacological effect of Diyu Shengbai Tablets on leucopenia,and its regulation on endogenous metabolites based on 1 H-NMR Metabolomics method,to explore its mechanism.Methods:4 T1 breast cancer-bearing mice were constructed,then 80 mg/kg cyclophosphamide was intraperitoneally injected to establish a leukopenia model caused by tumor chemotherapy.Mice were randomly divided into the control group,the model group and 0.14 g/kg Diyu Shengbai Tablets group.All mice were orally administered for 1 week.The traditional pharmacodynamic indexes(blood routine and organ index)were used to evaluate the effect of Diyu Shengbai Tablets.The serum samples were analyzed by 1H-NMR technology to find differential metabolites related to the effect of Diyu Shengbai Tablets,and analyze its key metabolic pathways,in order to explain the possible mechanism.Results:Compared with the control group,the leukocyte content in the model group was significantly reduced(P<0.01),and the spleen and thymus indexes were significantly reduced(P<0.01),and the liver index was significantly increased(P<0.05).Compared with the model group,WBC content was significantly increased in 0.14 g/kg Diyu Shengbai Tablets group(P<0.01),the organ indexes were significantly improved(P<0.05,P<0.01).Metabonomics results showed Diyu Shengbai Tablets significantly regained the levels of 8 differential metabolites(P<0.05 or P<0.01)by regulating the metabolic pathway of Glutamine,glutamic acid metabolism,nitrogen metabolism,arginine biosynthesis,alanine,aspartic acid and glutamic acid metabolism,etc.Conclusion:The main mechanism of Diyu Shengbai Tablets on improving leukopenia may be related to regulating Glutamine and glutamic acid metabolism,nitrogen metabolism,arginine biosynthesis,alanine,aspartic acid and glutamic acid metabolism,etc.

关 键 词：地榆升白片 白细胞减少症 核磁共振 代谢组学 通路分析 

分 类 号：R285.5[医药卫生—中药学]