联合应用缓激肽与罂粟碱开放血肿瘤屏障作用  

Joint effects of bradykinin and papaverine on blood-tumor barrier permeability in brain of rats

作　　者：徐畅[1] 刘坤[1] XU Chang;LIU Kun(School of Basic Medical Science,Shenyang Medical College,Shenyang,Liaoning Province 110034,China)

机构地区：[1]沈阳医学院基础医学院,辽宁沈阳110034

出　　处：《中国公共卫生》2018年第8期1117-1119,共3页Chinese Journal of Public Health

基　　金：国家级大学生创新创业训练计划项目(201510164007);辽宁省大学生创新创业训练计划项目(20151167);沈阳医学院大学生科研立项(20150807)

摘　　要：目的探讨缓激肽与罂粟碱(papaverine,PA)联合应用对血肿瘤屏障通透性和紧密连接(tight junctions,TJ)相关蛋白之闭锁小带蛋白1(ZO-1)表达的影响。方法应用大鼠胶质瘤模型,伊文思蓝(Evans blue,EB)渗透性实验检测血肿瘤屏障通透性,免疫组织化学法测定ZO-1蛋白表达,RT-PCR法测定ZO-1 m RNA表达。结果与对照组大鼠脑肿瘤组织中EB含量[(0.182±0.026)μg/g]比较,缓激肽、罂粟碱、缓激肽+罂粟碱组(联合组)大鼠脑肿瘤组织中EB含量[分别为(0.487±0.031)、(0.503±0.029)和(0.875±0.040)μg/g]均明显升高(P<0.01);与缓激肽、罂粟碱组比较,联合组大鼠脑肿瘤组织中EB含量进一步增加(P<0.01)。与对照组(0.379±0.011)比较,缓激肽、罂粟碱、联合组大鼠脑肿瘤组织中ZO-1蛋白表达[分别为(0.259±0.008)、(0.252±0.010)和(0.135±0.015)]均明显下降(P<0.01);与缓激肽、罂粟碱组比较,联合组大鼠脑肿瘤组织中ZO-1蛋白表达进一步降低(P<0.01)。与对照组(0.876±0.062)比较,缓激肽、罂粟碱、联合组大鼠肿瘤组织中ZO-1 m RNA表达[分别为(0.735±0.036)、(0.695±0.050)和(0.420±0.047)]均明显降低(P<0.01);与缓激肽、罂粟碱组比较,联合组大鼠脑肿瘤组织中ZO-1 m RNA表达进一步降低(P<0.01)。结论缓激肽与罂粟碱联合应用对血肿瘤屏障的开放作用具有协同效应,此作用与紧密连接相关蛋白ZO-1表达水平下调有关。Objective To study joint effects of bradykinin（BK） and papaverine（PA） on blood-tumor barrier（BTB）permeability and zonula occludens 1（ZO-1） expression. Methods Glioma model was established in Sprague-Dawley rats.BTB permeability was assessed by Evans blue（EB） extravasation method; the expression of ZO-1 protein and m RNA were determined with immunohistochemistry assay and reverse transcriptase-polymerase chain reaction. Results Significantly increased EB contents（0.487 ± 0.03, 0.503 ± 0.029, and 0.875 ± 0.040 μg/g） were detected in brain tissues of the rats administrated with BK, PA, and BK plus PA compared with that（0.182 ± 0.026 μg/g） in control rats（P〈0.01 for all） and the increase of EB content of the rats treated with BK plus PA was significantly higher than that of the rats treated with only BK or PA（both P〈0.01）. The expressions of ZO-1 protein in brain tumor tissues of the rats treated with BK, PA, and BK plus PA were 0.259 ± 0.008, 0.252 ± 0.010, and 0.135 ± 0.015 and all the expressions were significantly decreased in comparison with that（0.379 ± 0.011） of the control rats（all P〈0.01） and the decrease of the rats treated BK plus PA was significantly lower than that of the rats treated with only BK or PA（both P〈0.01）; significantly decreased ZO-1 m-RNA expression was also observed in brain tumor tissues of the rats exposed to BK（0.735 ± 0.036）, PA（0.695 ± 0.050）, and BK plus PA（0.420 ±0.047） than that（0.876 ± 0.062） of the control group（all P〈0.01） and the decrease in the rats exposed to BK plus PA was significantly lower than that in the rats only exposed to BK or PA（both P〈0.01）. Conclusion Administration of BK and PA have synergistic effect on the opening of BTB in rats and the effect may related to down-regulation of ZO-1 expression.

关 键 词：缓激肽 罂粟碱 血肿瘤屏障 闭锁小带蛋白1(ZO-1) 

分 类 号：R114[医药卫生—卫生毒理学]