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

作者：Pan, Long; Yao, Dun-Chen; Yu, Yu-Zhong; Li, Sheng-Jie; Chen, Bing-Jun; Hu, Gui-He; Xi, Chang; Wang, Zi-Hui; Wang, Hong-Yan; Li, Jian-Hua; Tu, Yong-Sheng^*

来源：Biochemical and Biophysical Research Communications, 2016, 478(4): 1602-1608.

DOI：10.1016/j.bbrc.2016.08.163

• ARDS
• Necroptosis
• Inflammation
• Necrostatin-1

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.

• 出版日期2016-9-30
• 单位广州医科大学