BRADYKININ SELECTIVELY OPENS BLOOD-TUMOR BARRIER IN EXPERIMENTAL BRAIN-TUMORS
BRADYKININ SELECTIVELY OPENS BLOOD-TUMOR BARRIER IN EXPERIMENTAL BRAIN-TUMORS
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DOI：
10.1038/jcbfm.1994.108
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发表时间：
1994-09-01
影响因子：
6.3
通讯作者：
BLACK, KL
中科院分区：
文献类型：
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作者：
INAMURA, T;BLACK, KL
与单纯颈动脉注射生理盐水相比，小剂量缓激肽(10微克/公斤/分)经RG2脑胶质瘤同侧颈动脉注入可显著增加肿瘤毛细血管对6种不同分子量示踪剂的通透性。颈动脉注射缓激肽对正常脑毛细血管通透性无明显影响。用于检测渗透性的示踪剂包括放射性标记的cr-氨基异丁酸(MW103)、蔗糖(MW5000)、菊粉(MW5000)、葡聚糖(mW70,000)、辣根过氧化物酶(Hrp)和伊文思蓝(EB)。渗透率用单向传递常数K-i(Mu L/g/min)表示。缓激素组与生理盐水组相比，AIB、蔗糖、菊粉和葡聚糖的通透性(K-I)分别为25.91+/-6.78和13.95+/-4.29(p<；0.01)，17.90+/-2.65和10.75+/-4.55(p<；0.01)，23.92+/-6.99和6.20+/-4.37(p<；和17.84+/-1.00vs.1.47+/-1.24(p<；0.001)(平均值+/-SD)。缓激素组RG2胶质瘤对高分子右旋糖苷(70,000)的渗透性是生理盐水组的12倍。颈动脉内注射缓激肽并没有显著增加肿瘤或脑组织的血容量，尽管它具有已知的血管扩张作用。颈动脉注射缓激肽对正常脑毛细血管通透性无明显影响。停止颈动脉内给药20分钟后，通透性增加的情况被逆转。用HRP和EB进行了电子显微镜和大体定性分析。颈动脉注射缓激肽可增加肿瘤组织内的HRP和EB，但不能增加正常组织内的HRP和EB。我们相信，颈动脉内注射缓激肽将是选择性地将抗肿瘤化合物输送到脑瘤的一种有用的技术。
Bradykinin, infused in low doses (10 mu g/kg/min) through the carotid artery ipsilateral to RG2 glioma in rats, significantly increased the permeability in tumor capillaries to six different tracers of varying molecular weights compared with intracarotid infusion of saline alone. Permeability in normal brain capillaries was not significantly increased by intracarotid bradykinin infusion. Tracers used to examined permeability included radiolabeled cr-aminoisobutyric acid (AIB; MW 103), sucrose (MW 342.3), inulin (MW 5000), and dextran (MW 70,000), horseradish peroxidase (HRP) and Evans blue (EB). Permeability was expressed as the unidirectional transfer constant K-i (mu l/g/min). The permeabilities (K-i) of tumors in the bradykinin group versus the control saline group for AIB, sucrose, inulin, and dextran were 25.91 +/- 6.78 vs. 13.95 +/- 4.29 (p < 0.01), 17.90 +/- 2.65 vs. 10.75 +/- 4.55 (p < 0.01), 23.92 +/- 6.99 vs. 6.20 +/- 4.37 (p < 0.01), and 17.84 +/- 1.00 vs. 1.47 +/- 1.24(p < 0.001), respectively (mean +/- SD). Permeability of RG2 gliomas to high molecular weight dextran (70,000) was 12-fold higher in the bradykinin group than in the saline infusion group. Intracarotid infusion of bradykinin did not significantly increase the blood volume in tumor or brain tissue despite its known vasodilative effect. The permeability of normal brain capillaries was unaffected by intracarotid bradykinin infusion. The increased permeability was reversed 20 min after stopping the intracarotid infusion. Electron microscopic and gross qualitative analysis was performed using HRP and EB. Intracarotid bradykinin infusion increased HRP and EB within tumor tissue but not normal tissue. We believe that intracarotid infusion of bradykinin will be a useful technique for selective delivery of antitumor compounds to brain tumors.