caveolin-1对低频超声辐照选择性开放血肿瘤屏障中occludin表达及分布的影响  

The effect of caveolin-1 on occludin expression in the selective opened bloodtumor barrier irradiated by low-frequency ultrasound

作　　者：宋阳[1] 郑晓娇[1] 薛一雪[2] 

机构地区：[1]中国医科大学基础医学院机能实验中心,辽宁沈阳110122 [2]中国医科大学基础医学院神经生物学教研室,辽宁沈阳110122

出　　处：《解剖科学进展》2017年第2期119-122,共4页Progress of Anatomical Sciences

基　　金：辽宁省科技厅项目(2014021086)

摘　　要：目的探讨低频超声辐照选择性开放血肿瘤屏障过程中,caveolin-1对occludin表达及分布的影响。方法 Western blot检测occludin的表达,测量跨内皮细胞电阻值检测血肿瘤屏障通透性,双重免疫荧光染色法检测caveolin-1及occludin在脑微血管及体外血肿瘤屏障内皮细胞内的定位表达。结果低频超声辐照后occludin表达及跨内皮细胞电阻随时间变化呈先下降后回升趋势,于低频超声辐照后1.5h,二者下降最为显著(P<0.01)。以低频超声辐照后1.5h为时间点,抑制caveolin-1的表达,occludin的表达增加(P<0.01),跨内皮电阻增高(P<0.05)。双重免疫荧光染色显示caveolin-1和occludin在正常和脑胶质瘤大鼠脑微血管共定位,在体外血肿瘤屏障内皮细胞膜上共定位;低频超声辐照后1.5h,caveolin-1在胞质中表达显著增多,并诱导occludin从胞膜转移至胞质。结论低频超声辐照选择性开放血肿瘤屏障的过程中,caveolin-1增加血肿瘤屏障通透性与下调occludin的蛋白表达并诱导其内化相关。Objective To explore the potential role of caveolin-1 in regulating the expression and the localization of occludin in the selective opened blood-tumor barrier（BTB） by use of low-frequency ultrasound（LFU） irradiation. Methods The expression of caveolin-1 was detected by Western blot and the permeability of BTB was measured by transepithelium electrical resistant（TEER）. The localization of caveolin-1 and occludin in brain microvessels of rats and in brain microvascular endothelial cells（BMECs） of the vitro BTB was examined by double immunofluorescence staining. Results The expression level of occludin and TEER showed a trend from decline to rise after LFU irradiation. The expression levels of occludin and TEER reached the lowest point at 1.5h after irradiation of LFU（P〈0.01）. 1.5h after LFU irradiation was taken as a specific point time, the expression level of occludin was significantly enhanced（P〈0.01）and TEER was increased after caveolin-1 was inhibited. The colocalization of caveolin-1 and occludin was detected in brain microvessels of normal or glioma rats and in BMECs. At 1.5h after irradiation of LFU, a remarkable increase of caveolin-1 expression in cytoplasm was found to be associated with the translocation of occludin from cell membrane to cytoplasm. Conclusion Under LFU irradiation of the selective opened BTB, increased permeability of BTB by caveolin-1 might be related to down-regulating the expression of occludin and triggering the intracellular trafficking of occludin.

关 键 词：血肿瘤屏障 低频超声 CAVEOLIN-1 OCCLUDIN 大鼠 

分 类 号：R730.23[医药卫生—肿瘤]