天然产物研究与开发 ›› 2025, Vol. 37 ›› Issue (2): 223-232.doi: 10.16333/j.1001-6880.2025.2.004 cstr: 32307.14.1001-6880.2025.2.004

• 研究论文 • 上一篇    下一篇

基于药效学和代谢组学研究当归补血汤不同提取物对溶血性贫血大鼠的作用

樊 秦1,2,3,王雅琼1,赵彩霞1,张志瑞1,张宏美1,宋 冰1*,阎教科4,戚欢阳5


  

  1. 1甘肃中医药大学;2甘肃中医药大学甘肃省中医药研究中心;3敦煌医学与转化教育部重点实验室;4兰州美尔康生物科技有限公司,兰州 730000;5厦门市健康医疗大数据中心(厦门市医药研究所) 厦门市天然药物研究与开发重点实验室,厦门 361008
  • 出版日期:2025-02-28 发布日期:2025-02-28
  • 基金资助:
    甘肃省高等学校创新基金(2022A-073);兰州市人才创新创业项目(2022-RC-44);敦煌医学与转化教育部重点实验室项目(DHYX21-09);厦门市科技局一般科技计划(3502Z20224004)

Effects of different extracts of Danggui Buxue Decoction on hemolytic anemia rats based on pharmacodynamics and metabolomics

FAN Qin1,2,3,WANG Ya-qiong1,ZHAO Cai-xia1,ZHANG Zhi-rui1,ZHANG Hong-mei1,SONG Bing1*,YAN Jiao-ke4,QI Huan-yang5   

  1. 1Gansu University of Chinese Medicine; 2Research Center of Traditional Chinese Medicine,Gansu University of Chinese Medicine; 3Key Laboratory of Dunhuang Medicine,Ministry of Education; 4Lanzhou Meierkang Biotechnology Co.,Ltd.,Lanzhou 730000,China; 5Xiamen Health and Medical Big Data Center (Xiamen Medicine Research Institute),Xiamen Key Laboratory of Natural Medicine Research and Development,Xiamen 361008,China

  • Online:2025-02-28 Published:2025-02-28

摘要:

运用动物模型和血浆代谢组学,探讨当归补血汤抗溶血性贫血作用的有效部位及其分子机制。将56只雄性Wistar大鼠随机分为7组,即为正常对照组(normal control group,NC)、模型组(model group,MOD)、阳性对照组(positive control group,PC),4个当归补血汤提取物给药组包括水提物组(water extract group,WE)、70%醇提物组(70% alcohol extract group,AE)、水提醇沉上清提取物组(water extraction and alcohol precipitation supernatant extract group,WASE)和水提醇沉组(water extraction and alcohol precipitation group,WEAP)。模型组和各给药组皮下注射2%乙酰苯肼(acetylphenylhydrazine,APH)建立溶血性贫血模型,通过测定血常规指标和促红细胞生成素(erythropoietin,EPO)含量评价不同给药组抗溶血性贫血效果;采用气相色谱-质谱联用仪(gas chromatography-mass spectrometer,GC-MS)技术结合多元统计分析鉴定代谢物,比较分析各给药组代谢轮廓及差异生物标志物,并构建其代谢通路;采用试剂盒测定各组大鼠血清中与氧化应激、炎症因子和造血调控相关因子的水平,对代谢通路的生物学功能进行验证。通过比较分析血常规指标和EPO含量,证明模型制备成功,综合评价表明WASE组抗溶血性贫血效果最好。代谢组学结果显示模型组与正常对照组代谢轮廓明显分离,WASE组代谢轮廓更趋向于正常对照组代谢轮廓。与正常对照组相比,溶血性贫血大鼠模型中涉及能量、氨基酸、糖和脂肪酸代谢有关的6条代谢通路受到影响,而WASE组可调节此6条代谢通路。与模型组比较,除PC组外,其余各给药组均能显著性降低血清中丙二醛(malondialdehyde,MDA)(P<0.01或P<0.05)、白细胞介素-6(interleukin-6,IL-6)(P<0.01或P<0.05)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)(P<0.01或P<0.05)和白细胞介素-2(interleukin-2,IL-2)含量(P<0.01或P<0.05),显著升高超氧化物歧化酶(superoxide dismutase,SOD)(P<0.01或P<0.05)和还原型谷胱甘肽(glutathione,GSH)水平(P<0.01或P<0.05),并且WASE组大鼠血清中MDA(P<0.01)和TNF-α 含量较其他给药组均显著降低(P<0.01或P<0.05)。由上可知WASE组治疗溶血性贫血效果最好,主要通过影响6条代谢通路调节机体能量代谢、抗氧化、抗炎和造血细胞功能作用,改善溶血性贫血模型大鼠代谢紊乱,达到治疗溶血性贫血的作用。


关键词: 当归补血汤提取物, 溶血性贫血, 代谢通路, 分子机制

Abstract:

The effective parts and molecular mechanism of Danggui Buxue decoction in anti-hemolytic anemia were studied with animal model and plasma metabolomics.Fifty-six male wistar rats were randomly divided into seven groups:normal control group (NC),model group (MOD),positive control group (PC),and four Danggui Buxue decoction extract administration group,which included water extract group (WE),70% alcohol extract group (AE),water extraction and alcohol precipitation supernatant extract group (WASE) and water extraction and alcohol precipitation group (WEAP).The model group and each treatment group were subcutaneously injected with 2% acetylphenylhydrazine (APH) to establish a hemolytic anemia model.The anti-hemolytic anemia effect of treatment group was evaluated by measuring blood routine indexes and erythropoietin (EPO) content.The significant different metabolites between groups were identified by gas chromatography-mass spectrometer (GC-MS) combined with multivariate statistical analysis,and their metabolic pathways were constructed.The levels of factors related to oxidative stress,inflammatory factors and hematopoietic regulation in serum of rats in each group were measured with kits.The comprehensive evaluation of pharmacodynamics showed that WASE group had the best anti-hemolytic anemia effect.Compared with the K group,6 metabolic pathways related to the metabolism of energy,amino acid,sugar and fatty acid were affected in the hemolytic anemia rat model,and these 6 metabolic pathways could be regulated in the WASE group.Compared with model group,except group PC,in the serum of other administration groups,the content of malondialdehyde (MDA),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) were all significantly decreased (P < 0.01 or P < 0.05),and the levels of superoxide dismutase (SOD) and glutathione (GSH) were all significantly increased (P < 0.01 or P < 0.05).However,the content of MDA (P< 0.01) and TNF-α (P < 0.01 or  P < 0.05) in serum of WASE group were significantly lower than those of other groups.All these showed that WASE group has the best effect for hemolytic anemia,which mainly regulated the body′s energy metabolism,antioxidant,anti-inflammatory and hematopoietic cell function by affecting six metabolic pathways,and improved the metabolic disorders of hemolytic anemia model rats,so as to treat hemolytic anemia.

Key words: extracts of danggui buxue decoction, hemolytic anemia, metabolic pathway, molecular mechanism ,

中图分类号:  R285