百草枯诱导大鼠肺微血管内皮细胞凋亡实验研究  

The experiment study of paraquat induced apoptosis of rat pulmonary microvascular endothelial cells

作　　者：姜文[1] 何庆[2] 

机构地区：[1]四川大学华西医院急诊医学科 [2]四川大学华西医院急诊医学科教授

出　　处：《世界急危重病医学杂志》2007年第5期2029-2030,共2页internationl journal of emergency and critical care medicine

摘　　要：[论文特点介绍]百草枯的肺毒性在于通过增加氧化应激导致肺损伤，而氧化应激可能是导致细胞凋亡的最后共同通路。众所周知，百草枯可以在体内外产生氧自由基损伤肺微血管内皮。然而，在百草枯所致的肺损伤中．百草枯能否诱导肺微血管内皮细胞的凋亡及其机制仍不清楚。近来已有研究显示百草枯可以诱导某些细胞的凋亡。在本研究中，检测了百草枯对培养的大鼠肺微血管内皮细胞的直接毒性和凋亡的影响，Background and objective Paraquat （PQ） is widely used as a universal herbicide and the frequent toxicity that causes human death. PQ causes lung injury by enhancing oxidative stress. Oxidative stress may be the common final passageway that many stimulants cause apoptosis. It is well known that PQ can generate O2 radicals and injure pulmonary microvascular endothelial cells （PMVECs） in vivo and in vitro. However, whether PQ-induces apoptosis of PMVECs and the mechanisms by which PQ causes acute lung injure is not known. Recent studies have shown that PQ can induce apoptosis of some cells. In the present study, we examined the direct toxic and apoptotic effects of PQ on cultured rat PMVECs, in order to study the mechanisms of PQ intoxication. Methods Primary cultures of male Sprague-Dawley rat PMVECs were identified. Cultured rat PMVECs were incubated with different concent- rations of PQ and different time periods. The toxic and apoptotic effects were studied by MTF method, DNA fragmentation （agarose gel electrophoresis）, morphology （DAPI staining）, and flow cytometry. Results Rat PMVECs were cultured successfully. It was found with MTF method that PQ inhibited the proliferation and metabolism of rat PMVECs in vitro in a dose- and time-dependent manner. Apoptotic DNA ladder were demonstrated by agarose gel electrophoresis. Apoptotic features such as chromatin condensation and nuclei fragmentation were shown by the morphological of the nuclei. Flow cytometry revealed subG0/1 peaks （PI staining）. Conclusions PQ could inhibite the proliferative activity and induce apoptosis of rat PMVECs in vitro. Apoptosis of rat PMVECs may be one of the mechanisms of PQ induced acute lung injury （ALI）.

关 键 词：肺微血管内皮细胞 内皮细胞凋亡 诱导大鼠 百草枯 实验研究 氧自由基损伤 氧化应激 共同通路 

分 类 号：R563[医药卫生—呼吸系统] R543.5[医药卫生—内科学]