特异性磷酸二酯酶抑制剂sildenafil增加缓激肽对血-肿瘤屏障的通透性

Specific phosphodiesterase inhibitor sildenafil increases the effect of bradykinin on blood-tumor barrier permeabil-ity

目的 研究新的cGMP特异性磷酸二酯酶sildenfil抑制剂是否能增加颈动脉灌注缓激肽对脑肿瘤的血-肿瘤屏障的通透性。方法 用放射自显影方法检测单独应用sildenfil,缓激肽以及sildenfil与缓激肽伍用时血-肿瘤屏障通透性的变化。结果sildenfil与缓激肽伍用与单独应用缓激肽相比较,能显著增加反映血-肿瘤屏障通透性的指标单向转运系数Ki值(P<O.O5)。经缓激肽灌流的肿瘤组织中cGMP含量显著增加(P<O.05)。结论特异性磷酸二酯酶抑制剂sildenafil与缓激肽伍用能显著增加血一肿瘤屏障的通透性,从而能够增加药物选择性地转运到脑肿瘤组织。cGMP可能是缓激肽选择性增加血-肿瘤屏障的重要因素之一。

Objective To study the effecr of specific phosphodiesterase inhibitor sildenafil on bradykinin induced opening of blood -tumor barrier. Methods The permeability of blood-tumor barrier was measured by au-toradiography in sildenfil, bradykinin and sildenfil +bradykinin groups,respectively. Results The unidirectional transfer constant Ki was increased significantly in .sildenfil + bradykinin group compared with bradykinin alone group(P<0.05). The concentration of cGMP in tumor tissue was increased after bradykinin perfusion(P<0. 05). Conclusion The permeability of blood-tumor barrier was increased significantly by using specific phosphodi esterase inhibitor sildenafil with bradykinin. cGMP plays a key role in the selective opening of blood-tumor barrier induced bv bradvkinin.