艾迪注射液对H22肝癌模型小鼠组织中阿霉素和阿霉醇分布的影响

Effect of Aidi injection on biodistribution of doxorubicin and doxorubicinol in mouse model of H22 hepatocellular carcinoma

目的研究艾迪注射液(ADI)对阿霉素(DOX)及其活性代谢产物阿霉素醇(DOXol)在H22肝癌模型小鼠体内组织分布的影响。方法建立H22肝癌移植瘤小鼠模型,将模型小鼠随机分成DOX单次给药组(SDOX组)、DOX多次给药组(MDOX组)和ADI联合MDOX组(AMDOX组)。三组小鼠均造模15d,于造模结束2 h时收集各组小鼠的血液、肿瘤、心、肝、肾、肺组织,样本处理后,采用超高效液相串联质谱法(UPLC-MS/MS)测定DOX和DOXol浓度,比较各组小鼠DOX和DOXol的组织分布情况。结果与SDOX组比较,MDOX组小鼠各组织中DOX和DOXol的含量均显著增加,差异有统计学意义(P<0.05);联合用药后,DOX和DOXol除了在肿瘤部位的积累量明显增加外,在其余组织中均表现出不同程度的降低趋势,差异有统计学意义(P<0.05)。结论ADI可能是通过增加肿瘤中DOX和DOXol浓度增强抗肿瘤能力,并且通过降低心脏中DOX和DOXol浓度、降低DOX的心脏毒性。

Objective To study the effect of Aidi injection(ADI)on biodistribution of doxorubicin(DOX)and its active metabolite doxorubicinol(DOXol)in mouse model of H22 hepatocellular carcinoma(HCC).Methods H22 HCC mouse model was established,and the model mice were randomly divided into single DOX(SDOX group),multiple DOX(MDOX group)and ADI combined MDOX(AMDOX group).It took 15 days to establish H22 HCC mouse model.Blood,tumor,heart,liver,kidney,and lung were collected at 2 hours after completing the modeling.The concentrations of DOX and DOXol were determined by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The biodistribution of DOX and DOXol were compared among three groups.Results Compared with SDOX group,the contents of DOX and DOXol in MDOX group were significantly increased(P<0.05).The contents of DOX and DOXol in the tumors were significantly increased,but displayed a decreased trend in the rest of tissues in AMDOX group(P<0.05).Conclusion ADI may enhance the antitumor ability by increasing the concentration of DOX and DOXol in the tumor and reduce the cardiotoxicity of DOX by decreasing the concentration of DOX and DOXol in the heart.