活性氧在MEHP致大鼠离体心脏损伤中的作用  

Study on the effect of oxidative stress on the cardiac injury induced by MEHP in rats

作　　者：王泽泽 刘诣[1] 周丽晓 张玉 何璇 赵丽娟[1] 张荣[1] 郭会彩[1] Wang Zeze;Liu Yi;Zhou Lixiao;Zhang yu;He Xuan;Zhao Lijuan;Zhang Rong;Guo Huicai(Department of Toxicology,School of Public Health,Hebei Medical University,Hebei Province Key Laboratory of Environment and Huamau Health,Shijiazhuang 050017,China)

机构地区：[1]河北医科大学公共卫生学院卫生毒理学教研室、河北省环境与人群健康重点实验室,石家庄050017 [2]河北省计划生育科学技术研究院、国家卫生和计划生育与优生重点实验室

出　　处：《中华劳动卫生职业病杂志》2018年第7期485-491,共7页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金资助项目（81473292）;河北省高层次人才资助项目（A2016005064）;河北省自然科学基金项目（B2018206283）

摘　　要：目的观察邻苯二甲酸二乙基已酯（MEHP）对大鼠离体心脏的损伤作用及其机制探讨。方法将35只SD大鼠随机分为对照组，3．125、6．250、12．500和25．000μmol／LMEHP组，5mmol／LNAC＋12．500μmol／LMEHP组，5mmol／LNAC＋25．00μmol／LMEHP组，每组5只。应用Langendorff大鼠离体心脏灌流技术，采用PL3508数据采集分析系统连续记录给予灌流液后0、5、10、15、20、25min这6个时间点处心率、左心室发展压（LVDP）、左室内压最大上升速率（dp/dtmax）、左室内压最大下降速率（dp/dtmin）及初始左心室舒张末压（LVEDP）并进行分析。生化法测定心脏流出液中乳酸脱氢酶（LDH）的含量；部分左心室组织用于组织病理学检查；DCFH—DA标记法检测不同组心肌细胞活性氧（ROS）水平。结果病理结果显示，与对照组比较，MEHP组心脏组织出现明显的水肿、炎性细胞浸润及心肌细胞坏死。与各自0min时心率值比较，随着MEHP浓度的增加，心率下降，且不同浓度间两两比较，心率呈现浓度依赖性下降，差异有统计学意义（P〈0．05）；6．250、12．500及25．000μmol/LMEHP灌流使大鼠离体心脏LVDP、dp／dtmax和dp／dtmin均明显降低，差异有统计学意义（P〈0．05），并且这种降低随灌流时间的延长而更加明显；而LVEDP在6．250、12．500及25．000μmol／LMEHP灌流时明显升高，差异有统计学意义（P〈0．05）；3．125μmol／LMEHP灌流时dp/dtmin在第10min和15min时明显升高，差异有统计学意义（P〈0．05）。心脏流出液中LDH随MEHP浓度的增加而升高。心脏组织ROS水平随着MEHP浓度的增加而明显升高。而给予抗氧化剂NAC，除心率外，NAC可部分拮抗MEHP所致的心肌收缩舒张功能、心脏流出液中LDH含量及病理改变。结论MEHP可引起大鼠离体心肌损伤，其机制可能与活性氧有关。Objective This study was to investigate the effects of MEHP on isolated rat heart and explore its mechanism. Methods The experiments were performed with Langendorff-perfused rat heart with a Langendorff apparatus. 35 SD rats were used in the experiment and there were 5 rats per group. MEHP at doses of 3.125, 6.250, 12.500 and 25.000 μmol/L were given to the hearts for 25 minutes. Effects of NAC at concentration of 5 mmol/L were evaluated by co-treatment with 12.500 or 25.000 μmol/L MEHP. Data was collected per 5 minutes for 25 minutes. The heart rate, LVDP, LVEDP, dp/dtmax, and dp/dtmin were measured and analyzed using a PL3508 Data Acquisition and Analysis System. 200 waves at least were required each time. LDH contents in heart lavage fluid were determined by photometric assays using the automated biochemical analyzer. A section of the heart tissue was used for histopathological examination. DCFH-DA method was used to detect the levels of reactive oxygen species in different groups of heart tissues. Results There was a concentration dependent decrease of heart rate （P〈0.05）. At concentrations of 6.250, 12.500 and 25.000 μmol/L, MEHP significantly decreased the LVDP, dp/dtmax and dp/dtmin （P〈0.05）, and this de- crease is more pronounced with perfusion time. As the MEHP was given up to 6.250, 12.500 and 25.000μmol/ L, a statistical significance was found in the increase of LVEDP（P〈0.05）. For dp/dtmin, a significant increase was observed at the concentration of 3.125 μmol/L when perfused with 10 and 15 min （P〈0.05）, but this in- crease disappeared over time. LDH in cardiac perfusate increased as the MEHP given a higher concentration （P〈0.05）. Compaled with the control group, Histopathological analysis showed edema of myocardial tissue and cells, and inflammatory cells infiltration and myocardial cells necrosis were obvious in the MEHP perfusion groups. Myocardial ROS levels of the four MEHP treatment groups were all significantly higher than that of con- trol group （P〈0.05）

关 键 词：邻苯二甲酸二乙基己酯 活性氧组分 心率 

分 类 号：R114[医药卫生—卫生毒理学]