表阿霉素诱导血管通透性改变的机制  

Effect of Epirubicin on Permeability of Cultured Endothelial Cells

作　　者：张京伟[1] 李明梅[1] 丁琼[2] 王莹[2] 胡鹏超[2] 汤梦婕[2] 魏蕾[2] 

机构地区：[1]武汉大学中南医院,武汉430071 [2]武汉大学基础医学院,武汉430071

出　　处：《微循环学杂志》2012年第3期14-16,75,共4页Chinese Journal of Microcirculation

基　　金：湖北省自然科学基金项目(2008CDB222)

摘　　要：目的:观察乳腺癌常规化疗药物表阿霉素(EPI)对血管内皮细胞通透性的影响,探讨其在静脉注射时造成血管渗漏的机制。方法:用0、0.1、1.0、10、100μg/mlEPI处理人脐静脉内皮细胞株HUVEC-CRL-1730,光学显微镜观察细胞形态改变,Transwell小室检测单层内皮细胞的通透性,MTT法检测细胞增殖效率,RT-PCR和Western blotting检测血管扩张刺激磷蛋白(VASP)mRNA和蛋白表达水平。结果:10μg/mlEPI处理内皮细胞24h后,与对照组相比,EPI能显著抑制内皮细胞增殖(P<0.05),细胞收缩、变形,单层内皮细胞通透性增加(P<0.05);同时,VASP mRNA和蛋白表达水平均降低(P<0.05)。结论:EPI静脉注射造成的血管渗漏可能与EPI抑制细胞增殖以及通过降低VASP蛋白表达导致的内皮细胞通透性增加有关。Objective: Epirubicin (EPI) is an anthracycline that routine used in chemotherapy of breast cancer, to evaluate the mechanism of EPI inducing vascular leakage, we observed the effects of it on permeability of cultured endothelial cells. Method: Treated cultured endothelial cells HUVEC-CRL-1730 with different concentration of EPI at 0,0.1,1.0,10.0,100.0μg/ml. And cell morphology changes were observed with optical microscope, meanwhile, a single layer of endothelial cells’ permeability was measured with Transwell assay, cell proliferation was evaluated with MTT assay, the expression of cytoskeleton-associated protein vasodilator stimulated phosphoprotein(VASP) mRNA and protein levels were detected by RT-PCR and Western blotting respectively. Results: After the endothelial cells were treated with 10.0μg/ml EPI for 24h, compared with the normal control group, EPI significantly inhibited the proliferation of endothelial cells (P<0.05), and cells contraction as well as intercellular gap was considerably widened. Transwell assay result also indicated that permeability of monolayer endothelial cells was increased (P<0.05), at the same time, the mRNA and protein expression levels of VASP was reduced significantly(P<0.05). Conclusion: The mechanism of EPI induced vascular leakage may correlate with an increasing of permeability in endothelial cells via inhibiting cell proliferation accompanied by reducing VASP protein expression.

关 键 词：通透性改变 血管渗漏 阿霉素诱导 临床并发症 肿瘤化疗药 抗肿瘤治疗 局部组织肿胀 器官功能障碍 

分 类 号：R779.120.2[医药卫生—眼科]