Necrostatin-1 protects against oleic acid-induced acute respiratory distress syndrome in rats

Necrostatin-1 protects against oleic acid-induced acute respiratory distress syndrome in rats
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Necrostatin-1 可预防油酸诱导的大鼠急性呼吸窘迫综合征

DOI:
10.1016/j.bbrc.2016.08.163
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发表时间:
2016-09-30
影响因子:
3.1
通讯作者:
Tu, Yong-Sheng
Tu, Yong-Sheng
中科院分区:
生物学4区
文献类型:
--
作者:
Pan, Long;Yao, Dun-Chen;Tu, Yong-Sheng

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Necroptosis is a recently discovered necrotic cell death which is regulated by receptor interacting protein kinase 1 (RIPK1) and RIPK3 under the stimulus of death signal and can be inhibited by necrostatin-1 (Nec-1) specifically. Therefore, the aim was to investigate the role of necroptosis in a rat model of acute respiratory distress syndrome (ARDS) induced by oleic acid (OA) and assess the effect of Nec-1 on lung injury in ARDS. Our results found that RIPK1, RIPK3 and mixed lineage kinase domain-like protein (MLKL) were abundantly expressed in rat lung tissues of OA-induced ARDS. Nec-1 pretreatment improved pulmonary function and attenuated lung edema dramatically in OA-induced ARDS rats. Furthermore, Nec-1 reduced RIPK1-RIPK3 interaction and down-regulated RIPK1-RIPK3-MLKL signal pathway, and inhibited inflammatory response by reducing neutrophil infiltration and protein leakage into lung tissue in OA-induced ARDS. Collectively, our study proves the intervention of necroptosis in OA induced ARDS. Moreover, our findings imply that Nec-1 plays an important role in the treatment of ARDS via inhibiting necroptosis and inflammation. (C) 2016 Elsevier Inc. All rights reserved.