卡托普利对百草枯致急性肺损伤的保护作用  

Protective effects of captopril on paraquat induced acute lung injury

作　　者：韩继媛[1] 张金萍[1] 孙鹏[1] 温宇英[1] 聂屾[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院急诊科,武汉430022

出　　处：《中华急诊医学杂志》2009年第10期1056-1059,共4页Chinese Journal of Emergency Medicine

基　　金：国家自然科学基金（30671783）

摘　　要：目的构建百草枯（paraquat，PQ）诱导的急性肺损伤细胞模型，探讨血管紧张素转化酶抑制剂卡托普利（captopril，CAP）对PQ中毒模型的保护作用。方法实验地点在武汉协和医院中心实验室，采用人脐静脉内皮细胞系（human umbilical vein endothelial cells，HUVECs），给予含不同浓度的PQ和CAP培养基孵育HUVECs，制备实验模型，MTT法检测细胞活性，半数成恬率判定模型成功与否。依据干预药物的不同确定实验分组：不予以药物干预为正常对照组（normal control group，NCG）；给予含400μmol／LPQ的培养基制备PQ损伤组；在PQ损伤同时予以CAP（10μmol／L）干预的为CAP保护组；因CAP干预时间的不同，分CAPA，CAPB，CAPC。检测在PQ损伤24h后检测培养基上清内SOD、MDA；免疫组织化学染色法检测亚细胞结构的变化；流式细胞仪检测细胞凋亡，数据采用（x±s）表示，应用SPSS16．0软件行统计学分析。结果MTT法检测PQ作用浓度，时间和CAP各组数值，采用单因素方差分析，F值分别为56．734，172．025，P〈0．01，成功构建了PQ模型及确定CAP干预浓度；与PQ组相比，CAP各组MDA含量降低（t分别为5．913，3．945，-3．426，P〈0．01），而SOD含量升高（t分别为5．463，-2．292，-1．297，P〈0．01）；细胞色素C含量明显减少及CAP组凋亡率降低。结论血管紧张素抑制剂CAP具有清除活性氧自由基作用，可拮抗PQ对HUVECs细胞的损伤作用，为PQ中毒的基础研究和临床治疗提供思考。Objective To establish paraquat（PQ）induced acute lung injury models induced by paraquat （PQ）, and to study the protective effects of angiotensian converting enzyme inhibitors （ACEI） with captopril （CAP） on the PQ posioning. Method All experiments were made in the central laboratory of Union Hospital. Human umbilical vein endothelial cells （HUVECs） were incubated with different concentration of paraquat and captopril to establish experimental models. Half of cell survival rate detected with MTT assay to judge whether the model was successful or not. Three groups were divided according to the different drug. application： normal control group without any drug intervetion, PQ group expensed to paraquat with the concentration of 400μmol/L and CAP group additionally exposed to captopril with concentration of 10μmol/L, which was repartitioned to three groups （CAPA, CAPB and CAPC） according to the different intervention time. The supernatant was collected to measure the concentration of malondialdehyde（MDA） and superoxide dismutase （SOD） after PQ injury for 24 hours, cytochrome C detected by intmunocytochemistry and apoptosis detected by flow cytometry. Data were expressed as mean ＋ standard error of the mean （ x ＋ s ）. Statistical analysis was carried out with the soft SPSS 16.0. Results MTT assay detected the concentration ＆ time of PQ intervention and the data of CAP groups, using the single-reseason variance analysis, F value were 56. 734,172. 025, P 〈 0.01 respectively, thus to successfully construct the PQ model and determine the concentration of CAP intervention groups. Relative to the PQ group, MDA as well as levels of cytochrome C of the CAP group were significantly decreased （ t = 5. 913,3. 945, - 3. 426, P 〈 0.01 ） ; while SOD were markedly increased （ t = 5. 463, - 2. 292, - 1. 297, P 〈 0.01 ）. It also showed that captopril markedly decreased PQ induced the rate of HUVECs apoptosis, the percentage of PQ group apoptosis was 46.1%, while CAP groups apo

关 键 词：百草枯 卡托普利 肺损伤 血管紧张素转化酶抑制剂 巯基 人脐静脉内皮细胞 细胞凋亡 中毒 

分 类 号：R96[医药卫生—药理学]