Inhibition of Secretory Phospholipase A2 Activity Attenuates Acute Cardiogenic Pulmonary Edema Induced by Isoproterenol Infusion in Mice After Myocardial Infarction
Inhibition of Secretory Phospholipase A2 Activity Attenuates Acute Cardiogenic Pulmonary Edema Induced by Isoproterenol Infusion in Mice After Myocardial Infarction
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DOI：
10.1097/fjc.0b013e3181ef1aab
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发表时间：
2010-10-01
影响因子：
3
通讯作者：
Kugiyama, Kiyotaka
中科院分区：
文献类型：
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作者：
Kawabata, Kenichi;Fujioka, Daisuke;Kugiyama, Kiyotaka
几种类型的分泌型磷脂酶A（2）（sPLA（2））在肺组织中表达，产生可能引起肺水肿的各种类花生酸。本研究检测了抑制sPLA（2）活性是否减轻小鼠急性心源性肺水肿。在C57 BL/6 J雄性小鼠中，通过左冠状动脉结扎造成心肌梗死后2周，持续静脉输注异丙肾上腺素（ISP）（10 mg/kg/h），增加心率，诱导急性心源性肺水肿。在ISP输注前，单次腹膜内注射100 mg/kg LY 374388（抑制sPLA（2）活性的LY 329722前药）或溶媒。心肌梗死后输注ISP可引起肺组织间质和肺泡水肿。此外，它还增加了肺/体重比、通过伊文思蓝外渗法评价的肺血管通透性、sPLA的肺活性（2）以及血栓素A（2）和白三烯B-4的肺含量。LY 374388处理显著减弱了这些变化。在Kaplan-Meier分析中，LY 374388处理小鼠心肌梗死后ISP输注期间的存活率显著高于溶剂处理小鼠。用sPLA（2）活性的另一种抑制剂对溴苯甲酰甲基溴获得了类似的结果。总之，抑制sPLA（2）活性可抑制急性心源性肺水肿。
Several types of secretory phospholipase A(2) (sPLA(2)) are expressed in lung tissue, yielding various eicosanoids that might cause pulmonary edema. This study examined whether inhibition of sPLA(2) activity attenuates acute cardiogenic pulmonary edema in mice. Acute cardiogenic pulmonary edema was induced in C57BL/6J male mice by an increase in heart rate with continuous intravenous infusion of isoproterenol (ISP) (10 mg/kg/h) at 2 weeks after the creation of myocardial infarction by left coronary artery ligation. Just before ISP infusion, a single intraperitoneal injection of 100 mg/kg LY374388, a prodrug of LY329722 that inhibits sPLA(2) activity, or vehicle was administered. The ISP infusion after myocardial infarction induced interstitial and alveolar edema on lung histology. Furthermore, it increased the lung-to-body weight ratio, pulmonary vascular permeability evaluated by the Evans blue extravasation method, lung activity of sPLA(2), and lung content of thromboxane A(2) and leukotriene B-4. These changes were significantly attenuated by LY374388 treatment. In Kaplan-Meier analysis, the survival rate during the ISP infusion after myocardial infarction was significantly higher in LY374388- than in vehicle-treated mice. Similar results were obtained with another inhibitor of sPLA(2) activity, para-bro mophenacyl bromide. In conclusion, inhibition of sPLA(2) activity suppressed acute cardiogenic pulmonary edema.