Protection by 20-5,14-HEDGE against surgically induced ischemia reperfusion lung injury in rats.
Protection by 20-5,14-HEDGE against surgically induced ischemia reperfusion lung injury in rats.
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DOI：
10.1016/j.athoracsur.2011.08.074
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Jacobs ER
中科院分区：
文献类型：
--
作者：
Ali I;Gruenloh S;Gao Y;Clough A;Falck JR;Medhora M;Jacobs ER
We previously reported that the cytochrome P450 product 20-hydroxyeicosatetraenoic acid has prosurvival effects in pulmonary artery endothelial cells and ex vivo pulmonary arteries. We tested the potential of a 20-hydroxyeicosatetraenoic acid analog N-[20-hydroxyeicosa-5(Z),14(Z)-dienoyl]glycine (20-5,14-HEDGE) to protect against lung ischemic reperfusion injury in rats. Furthermore, we examined activation of the innate immune system components high mobility group box 1 (HMGB1) and toll-like receptor 4 in this model as well as the effect of 20-5,14-HEDGE on this signaling pathway. Sprague Dawley rats treated with 20-5,14-HEDGE or vehicle were subjected to surgically induced, unilateral lung ischemia for 60 minutes followed by reperfusion for two hours in vivo. Injury was assessed histologically by hematoxylin and eosin, and with identification of myeloperoxidase immunohistochemically. HMGB1 and toll-like receptor 4 proteins were identified by western blot. Caspase 3 activity or 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a yellow tetrazole incorporation were used to measure apoptosis and cell survival. IR injury evoked atelectasis and hemorrhage, an influx of polymorphonuclear cells, and increased toll-like receptor 4 and HMGB1 expression. Caspase 3 activity was increased and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide incorporation was decreased. 20-5,14-HEDGE protected against each of these endpoints including infiltration of polymorphonuclear cells, with no changes in caspase 3 activity in other organs. Lung IR produces apoptosis and activation of the innate immune system including HMGB1 and toll-like receptor 4 within two hours of reperfusion. Treatment with 20-5,14-HEDGE decreases activation of this response system, and salvages lung tissue.
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影响因子：
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影响因子：
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DOI：
10.1152/ajpheart.01087.2008
发表时间：
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影响因子：
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作者：
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通讯作者：
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