马兜铃酸致血管内皮细胞毒性及羟苯磺酸钙的拮抗作用  

Aristolochic acid-induced endothelial cell injury and the mechanism of calcium dobesilate antagonism

作　　者：邓婧宜[1] 冯江敏[1] 孙立[1] 栗霄立[1] 姚丽[1] 李子龙[1] 王禹[1] 邹杰[1] 王力宁[1] 

机构地区：[1]中国医科大学附属第一医院肾内科,辽宁沈阳110001

出　　处：《中国医师杂志》2009年第7期913-916,共4页Journal of Chinese Physician

摘　　要：目的证实马兜铃酸（AA）能使血管内皮细胞（VEC）胞内钙离子（[Ca^2＋]i）超载，致VEC损伤，而羟苯磺酸钙有拮抗作用。方法体外培养人脐静脉内皮细胞系（HUVEC），用马兜铃酸钠（AA—Na）和羟苯磺酸钙处理，设对照组、AA组、干预组三组。倒置显微镜及透射电镜观察细胞形态及超微结构改变，ELISA法测定细胞培养上清液中血栓调节蛋白（TM），FLuo-3钙离子探针检测HUVEC（[Ca^2＋]i）浓度变化。结果与对照组相比，AA组TM值和平均（[Ca^2＋]i）浓度明显升高（P〈0．05）。与AA组相比，干预组羟苯磺酸钙浓度为25、50μM时，TM值和平均（[Ca^2＋]i）浓度明显降低（P〈0．05）；与对照组相比，AA组细胞内质网池状扩张。线粒体嵴缺损。而干预组细胞内质网、线粒体形态均有改善。结论AA—Na能使VEC钙超载，致内皮细胞破坏，TM增加，内质网和线粒体破坏；羟苯磺酸钙可以通过保护内质网、线粒体，减少VEC钙超载，保护VEC。Objective To prove aristolochic （AA） caused vascular endothelial cells （VEC） injury via intracellular calcium overloa- ding and investigate the mechanism of calcium dobesilate antagonism. Methods Human umbilical vein endothelial ceils （HUVEC） were cultured in vitro, and randomly divided into three groups： Control group, AA group, intervention group. Microscope and transmission electron microscopy were used to observe changes of cell morphology and uhrastructure. ELISA method were applied to determine thrombomodulin （TM） in cell culture supernatant, fluorescent indicator FLuo-3/AM and intracellnlar calcium concentration （ [ Ca^2＋ ]. Results TM value and average [ Ca^2 ＋ ] i of AA group were significantly higher than that of control group （ P 〈 0.05 ）. Compared with the AA group, when the concentration of calcium dobesilate was 25 μM or 50 μM, TM value and average [ Ca^2＋ ] significantly decreased in intervention group （ P 〈 0. 05）. Compared with control group, endoplasmic reticulum was pool expansion shaped, and mitochondrial cristae was absent in AA group cells. Endoplasmic reticulum and mitochondria patterns in the intervention group cells showed some improvement, compared with AA group. Conclusion AA induced VEC calcium overloading, TM secretion and injury of endothelial cells, endoplasmic reticulum and mitochondria destruction. Dobesilate calcium could protect endoplasmic reticulum and mitochondria and reduce AA induced VEC calcium over- loading, and these could protect VEC.

关 键 词：马兜铃酸/副作用 内皮 血管/药物作用/损伤 羟苯磺酸钙/药理学 

分 类 号：R28[医药卫生—中药学]