Nomura T, Inamura T, Black K L
Brain Research Institute, Johnson Comprehensive Cancer Center, UCLA Medical Center 90024.
Brain Res. 1994 Oct 3;659(1-2):62-6. doi: 10.1016/0006-8993(94)90863-x.
This study investigated the effects of bradykinin on blood-tumor barrier (BTB) permeability in transplanted 9L gliosarcomas (9L) and C6 gliomas (C6) in rats. Permeability, expressed as the unidirectional transfer constant, Ki (microliter/g/min), was measured by quantitative autoradiography. Tracers used to examined permeability included radiolabeled alpha-aminoisobutyric acid ([14C]AIB), sucrose ([14C]sucrose) and dextran ([14C]dextran). Intracarotid infusion of bradykinin (10 mg/kg/min) significantly increased the BTB permeability in both 9L and C6 tumors to [14C]AIB and [14C]sucrose, but did not increase permeability to [14C]dextran. Blood-brain barrier (BBB) permeability in normal (non-tumor) brain was not significantly increased to any of the tracers by intracarotid bradykinin infusion. Ki values for [14C]AIB, [14C]sucrose and [14C]dextran of 9L tumors in the bradykinin group versus control group were 41.6 +/- 12.6 vs. 24.8 +/- 6.30 (P < 0.02), 17.5 +/- 9.34 vs. 9.05 +/- 4.36 (P < 0.05), and 3.90 +/- 2.59 vs. 2.42 +/- 1.76, respectively (mean +/- S.D.). Ki values to [14C]AIB, [14C]sucrose and [14C]dextran of C6 tumors in the bradykinin group versus control group were 41.4 +/- 19.0 vs. 19.5 +/- 11.4 (P < 0.01), 18.0 +/- 8.88 vs. 7.06 +/- 3.05 (P < 0.01), and 4.07 +/- 1.45 vs. 2.27 +/- 1.26, respectively (mean +/- S.D.). Intracarotid infusion of bradykinin did not significantly increase the blood volume in tumor or brain tissue despite its known vasodilative effect. Intracarotid infusion of bradykinin may be a useful technique for selective delivery of compounds to brain tumors.
本研究调查了缓激肽对大鼠移植性9L胶质肉瘤（9L）和C6胶质瘤（C6）中血肿瘤屏障（BTB）通透性的影响。通透性以单向转运常数Ki（微升/克/分钟）表示，通过定量放射自显影法进行测量。用于检测通透性的示踪剂包括放射性标记的α-氨基异丁酸（[14C]AIB）、蔗糖（[14C]蔗糖）和右旋糖酐（[14C]右旋糖酐）。颈内动脉输注缓激肽（10毫克/千克/分钟）显著增加了9L和C6肿瘤对[14C]AIB和[14C]蔗糖的BTB通透性，但未增加对[14C]右旋糖酐的通透性。颈内动脉输注缓激肽后，正常（非肿瘤）脑组织对任何示踪剂的血脑屏障（BBB）通透性均未显著增加。缓激肽组与对照组9L肿瘤中[14C]AIB、[14C]蔗糖和[14C]右旋糖酐的Ki值分别为41.6±12.6对24.8±6.30（P<0.02）、17.5±9.34对9.05±4.36（P<0.05）和3.90±2.59对2.42±1.76（平均值±标准差）。缓激肽组与对照组C6肿瘤中[14C]AIB、[14C]蔗糖和[14C]右旋糖酐的Ki值分别为41.4±19.0对19.5±11.4（P<0.01）、18.0±8.88对7.06±3.05（P<0.01）和4.07±1.45对2.27±1.26（平均值±标准差）。尽管缓激肽具有已知的血管舒张作用，但颈内动脉输注缓激肽并未显著增加肿瘤或脑组织中的血容量。颈内动脉输注缓激肽可能是一种将化合物选择性递送至脑肿瘤的有用技术。
