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向颈动脉输注三油酸甘油酯乳剂可增加脑对抗癌药物的通透性。

Triolein Emulsion Infusion Into the Carotid Artery Increases Brain Permeability to Anticancer Agents.

作者信息

Kim Hak Jin, Kim Yong-Woo, Choi Seon Hee, Cho Byung Mann, Bandu Raju, Ahn Hyun Soo, Kim Kwang Pyo

机构信息

*Department of Radiology, College of Medicine, Pusan National University, Biomedical Research Institute, Pusan National University Hospital, Pusan, South Korea;‡Department of Preventive Medicine, College of Medicine, Pusan National University, Yangsan, South Korea;§Department of Applied Chemistry and Institute of Natural Sciences, Kyung Hee University, Yong-in, South Korea.

出版信息

Neurosurgery. 2016 May;78(5):726-33. doi: 10.1227/NEU.0000000000001104.

Abstract

BACKGROUND

Triolein emulsion infusion into the carotid artery has been reported to induce temporary and reversible opening of the blood-brain barrier by increasing vascular permeability.

OBJECTIVE

To evaluate the effect of triolein emulsion infusion on brain permeance by anticancer agents.

METHODS

In the doxorubicin study. 2.4 mg/kg doxorubicin was injected immediately after triolein emulsion (1%, 1.5%, and 2%) infusion into rabbit carotid arteries. Two hours later, bilateral hemispheres and eyeballs were harvested, and doxorubicin concentrations were measured fluorometrically. Doxorubicin ratios of ipsilateral/contralateral hemispheres were compared with those of doxorubicin controls by use of the Kruskal-Wallis test followed by the Dunn test. In the cisplatin study, 10 mg/kg cisplatin was injected immediately after 2% triolein emulsion infusion into rat carotid arteries. Ipsilateral hemispheres were harvested 2, 6, 12, 24, and 36 hours after treatment. Time-dependent cisplatin concentrations were determined by liquid chromatography/electrospray ionization-tandem mass spectrometry/mass spectrometry.

RESULTS

Doxorubicin concentrations were significantly higher in ipsilateral hemispheres and eyeballs in all 3 triolein treatment groups than in doxorubicin controls. In the cisplatin study, cisplatin concentrations in the ipsilateral hemispheres peaked at 6 hours after infusion of cisplatin.

CONCLUSION

Brain permeance to anticancer agents was increased by triolein emulsion infusion, which suggests that triolein infusion might be a useful adjuvant treatment for brain tumors.

摘要

背景

据报道,向颈动脉输注三油酸甘油酯乳剂可通过增加血管通透性诱导血脑屏障暂时且可逆的开放。

目的

评估三油酸甘油酯乳剂输注对抗癌药物脑通透性的影响。

方法

在阿霉素研究中,向兔颈动脉输注三油酸甘油酯乳剂(1%、1.5%和2%)后立即注射2.4mg/kg阿霉素。两小时后,采集双侧半球和眼球,采用荧光法测量阿霉素浓度。使用Kruskal-Wallis检验和Dunn检验将同侧/对侧半球的阿霉素比率与阿霉素对照组进行比较。在顺铂研究中,向大鼠颈动脉输注2%三油酸甘油酯乳剂后立即注射10mg/kg顺铂。治疗后2、6、12、24和36小时采集同侧半球。通过液相色谱/电喷雾电离-串联质谱/质谱法测定顺铂浓度的时间依赖性。

结果

在所有3个三油酸甘油酯治疗组中,同侧半球和眼球中的阿霉素浓度均显著高于阿霉素对照组。在顺铂研究中,同侧半球中的顺铂浓度在输注顺铂后6小时达到峰值。

结论

三油酸甘油酯乳剂输注可增加抗癌药物的脑通透性,这表明三油酸甘油酯输注可能是脑肿瘤的一种有用辅助治疗方法。

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