比较卡铂盆腔动脉化疗栓塞与单纯动脉灌注化疗的动物实验研究

Comparison of Pelvic Transarterial Chemoembolization with Lipiodol Ultra-fluid Carboplatin and Transarterial Carboplatin through Experiment in Dogs

背景与目的:动脉灌注化疗与动脉栓塞可提高肿瘤组织局部药物浓度和延长药效时间,但哪一种方法在临床药代动力学上更有优势,目前尚无定论。本研究的目的是比较超液态碘油卡铂盆腔动脉化疗栓塞与卡铂单纯动脉灌注化疗后,犬子宫组织及血浆中铂(Pt)离子浓度的分布。方法:选择实验用雌犬14只,随机分为盆腔动脉化疗栓塞组(A组)7只和盆腔动脉单纯灌注组(B组)7只。A、B组分别将卡铂(12mg/kg)溶于超液态碘油(0.2ml/kg)和5%葡萄糖(0.2ml/kg)中,注入双髂内动脉。然后在不同的时间点分别取子宫组织及静脉血,用原子吸收光谱法测定上述标本内的Pt离子浓度。结果:(1)A、B两组子宫组织Pt离子浓度曲线均为单峰曲线,峰值分别为(215.0±17.6)μg/g和(211.3±40.1)μg/g,两组无显著性差异(P>0.05)。(2)A、B两组子宫组织Pt离子药时曲线下面积(AUC0～240min)分别为(13.9±3.9)mg·min·g-1和(5.9±0.6)mg·min·g-1,两组有显著性差异(P<0.01)。(3)A、B两组血浆中Pt离子峰值分别为(8.7±12.5)μg/g和(16.7±3.6)μg/g,AUC0～240min分别为(0.5±0.1)mg·min·g-1和(1.2±0.4)mg·min·g-1,均有显著性差异(P<0.01)。结论:与卡铂单纯动脉灌注化疗相比,动脉化疗栓塞能有效提高并保持局部组织内的Pt浓度,降低血浆中Pt浓度。

BACKGROUND &OBJECTIVE: Transarterial chemoembolization, based on t ransarterial chemotherapy, is a new treatment for malignant neoplasms. This stud y was to investigate distribution of platinum (Pt) in blood and uterine tissue a fter infusing different carboplatin arterially. METHODS: Fourteen female dogs we re randomly divided into 2 groups: embolizational group (group A, 7 dogs),and ch emotherapy group (group B, 7 dogs). In group A, carboplatin (12 mg/kg), mingled with lipidol ultra-fluid (0.2 ml/kg), was injected into dogsiliac arteries. I n group B, carboplatin (12 mg/kg), dissolved in 5%glucose, was injected into th e same arteries.The uterine tissues and blood samples were collected at differen t time points, concentrations of Pt in samples were measured by atomic absorptio n method. RESULTS: Peak concentration of Pt in uterine tissues of group A was (2 15.0±17.6) 靏/g, that of group B was (211.3靏/g (P >0.05), the peak a ppeared at 0 min in both groups. Area under concentration-time curve (AUC) of P t in tissues of group A was (13.9±3.9) mg·min·g-1,significantly larger than that of group B (5.9±0.6) mg·min·g-1. Peak concentration of Pt in plasma of group A was (8.7±12.5) 靏/g, that of group B was (16.7靏/g. AUC0-240m in was (0.5±0.1) mg·min·g-1 in group A,and (1.2±0.4) mg·min·g-1 in group B (P< 0.05). CONCLUSION: Compared with arterial chemotherapy, arterial chemo-e mbolization may result in higher Pt concentration in local area, and lower Pt co ncentration in plasma, it may reduce the systemic toxicities, and enhance local effect on tumor.