血必净注射液与阿奇霉素联用在急性肺炎小鼠及巨噬细胞中的药动学相互作用  

Study on pharmacokinetic interaction by the combination of Xuebijing Injection and Azithromycin in acute pneumonia mouse and inflammation cells

作　　者：王瑞瑞 刘小梅 王晓明[1] 黄宇虹[2] 潘桂湘 WANG Ruirui;LIU Xiaomei;WANG Xiaoming;HUANG Yuhong;PAN Guixiang(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300250,China)

机构地区：[1]天津中医药大学,天津301617 [2]天津中医药大学第二附属医院,天津300250

出　　处：《天津中医药大学学报》2024年第9期798-803,共6页Journal of Tianjin University of Traditional Chinese Medicine

基　　金：天津市教委重点课题项目(2023ZD033)。

摘　　要：[目的]研究血必净注射液(简称XBJ)和阿奇霉素(AZM)联用前后,中药中的主要成分羟基红花黄色素A(HSYA)、芍药苷(PE)及AZM在急性肺炎小鼠模型整体动物水平及细胞水平上的药代动力学特征变化。[方法]使用脂多糖(LPS)建立急性肺炎小鼠及炎性小鼠单核巨噬细胞RAW264.7细胞模型,采用超高效液相色谱-三重四极杆质谱联用技术,使用Waters ACQUITY UPLC BEH C_(18)色谱柱(100 mm×2.1 mm,1.7μm),以0.1%甲酸水-乙腈为流动相体系,梯度洗脱,进样量2μL,流速0.3 mL/min,分别在正、负离子模式下,对血浆、肺组织、细胞样品进行质谱分析。[结果]AZM与XBJ联合用药后,在模型动物整体水平上,AZM、HSYA和PE在血浆中的药时曲线下面积(AUC)均升高,差异具有统计学意义(P<0.05),同时AZM与HSYA在血浆中的药峰浓度(Cmax)和达峰时间(Tmax)提高,差异具有统计学意义(P<0.05),以及三者在肺组织中的AUC也升高,差异具有统计学意义(P<0.01);在细胞水平上,AZM在RAW264.7细胞中的AUC升高,差异具有统计学意义(P<0.01),HSYA和PE在细胞中的AUC变化不明显,差异无统计学意义(P>0.05)。[结论]AZM与XBJ联合用药后,两者存在药动学相互作用。[Objective]To determine the pharmacokinetic properties of combination of Xuebijing Injection and Azithromycin,Hydroxy safflower yellow A and Paeoniflorin by liquid chromatography-mass spectrometry/mass spectrometry(LC-MS/MS)on acute pneumonia animal and cells level.[Methods]Acute pneumonia mouse and inflammation cells model were established by lipopolysaccharides(LPS).The chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C_(18)(100 mm×2.1 mm,1.7μm)column;The mobile phase was consisted of 0.1%formic acid water-formic acid acetonitrile at a flow rate of 0.3 mL/min with gradient elution,the mass spectrums were scanned by Essential Science Indicators(ESI)+and ESI-multiple reaction monitoring mode.[Results]With respect to the overall pharmacokinetics in model animals,the Area Under the Curve(AUC)of Azithromycin,Hydroxy safflower yellow A and Paeoniflorin were significantly increased(P<0.05),Cmax and Tmax of Azithromycin,Hydroxy safflower yellow A were significantly increased(P<0.05)and the AUC of lung tissue also increased(P<0.01).Based on cell level pharmacokinetics,the AUC of Azithromycin in RAW264.7 cells increased significantly(P<0.01),while the AUC of Hydroxy safflower yellow A and Paeoniflorin in cells did not change significantly(P>0.05).[Conclusion]There was a pharmacokinetic interaction after the combination of azithromycin and Xuebijing,and the pharmacokinetic characteristics of the cells were significantly changed.

关 键 词：血必净注射液 阿奇霉素 中西药联用 药动学相互作用 

分 类 号：R563.1[医药卫生—呼吸系统]