钙激活性钾通道在缓激肽选择性开放血脑肿瘤屏障机制中的大鼠在体研究

目的:探讨钙激活性钾通道(calciumactivatedpotassiumchannel,KCa)在缓激肽(bradykininBK)选择性开放血脑肿瘤屏障(bloodbraintumorbarrier,BTB)中的作用。方法:建立大鼠脑胶质瘤模型,颈内动脉分别灌注BK、KCa通道激动剂NS1619以及灌注BK后再灌注KCa通道阻断剂IBTX,取肿瘤标本电镜观察毛细血管内皮细胞的变化;颈内动脉灌注BK后采用免疫组化ABC法和Westernblot法测定肿瘤组织KCa通道蛋白的分布和含量的变化。结果:大鼠脑胶质瘤模型经颈内动脉分别灌注BK和NS1619后,肿瘤毛细血管内皮细胞的吞饮小泡增加,依次灌注BK和IBTX后,未观察到肿瘤毛细血管内皮细胞的吞饮小泡增加;脑胶质瘤大鼠模型经颈内动脉灌注BK后,其肿瘤内血管内皮细胞的KCa通道蛋白增加,且灌注后10min增加最为显著。结论:KCa通道蛋白的表达增多可能是BK选择性开放BTB机制中的重要因素之一。

Study of calcium-activated potassium channel in the mechanism of bradykinin selectively opening blood-brain tumor barrier in rat

OBJECTIVE:To investigate the role of calcium-activated potassium channel (KCa) in bradykinin (BK) selectively opening blood-brain tumor barrier. METHODS: After rat glioma model was established, BK,KCa channel excitomotor NS1619 and blocker IBTX following BK were respectively infused through rat internal carotid artery, the change of capillary endothelium cell in tumor sample was observed by electron microscope. After BK was infused through internal carotid artery, the distribution and content of KCa channel protein in glioma were determined by using the methods of immunohistochemistry and Western blot.RESULTS: The pinocytosis bullule in capillary endothelium cell in the tumor sample was increased after infused BK and NS1619, the pinocytosis bullule was not increased after infused BK and IBTX. The content of KCa channel protein in capillary endothelial cell in glioma was increased after infused BK through internal carotid artery, and the increasing in 10 min was the most significant. CONCLUSION: The increasing of expression of KCa channel protein of capillary endothelial cell in glioma is probably one of the important factors in BK selectively opening blood-brain tumor barrier.