title: Necrostatin-1 protects against oleic acid-induced acute respiratory distress syndrome in rats.
abstract: 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.
authors: Department of Physiology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 511436, China; The Third Clinical Medical College, Guangzhou Medical University, Guangzhou 511436, China.
authors: Long
authors: L
authors: Pan
authors: Department of Physiology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 511436, China; The Third Clinical Medical College, Guangzhou Medical University, Guangzhou 511436, China.
authors: Dun-Chen
authors: DC
authors: Yao
authors: Department of Physiology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 511436, China; The Third Clinical Medical College, Guangzhou Medical University, Guangzhou 511436, China.
authors: Yu-Zhong
authors: YZ
authors: Yu
authors: Department of Physiology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 511436, China; The First Clinical Medical College, Guangzhou Medical University, Guangzhou 511436, China.
authors: Sheng-Jie
authors: SJ
authors: Li
authors: Department of Physiology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 511436, China; The Third Clinical Medical College, Guangzhou Medical University, Guangzhou 511436, China.
authors: Bing-Jun
authors: BJ
authors: Chen
authors: Department of Physiology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 511436, China; The Third Clinical Medical College, Guangzhou Medical University, Guangzhou 511436, China.
authors: Gui-He
authors: GH
authors: Hu
authors: Department of Physiology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 511436, China; The Third Clinical Medical College, Guangzhou Medical University, Guangzhou 511436, China.
authors: Chang
authors: C
authors: Xi
authors: Department of Physiology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 511436, China; The Second Clinical Medical College, Guangzhou Medical University, Guangzhou 511436, China.
authors: Zi-Hui
authors: ZH
authors: Wang
authors: Department of Pathology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 511436, China.
authors: Hong-Yan
authors: HY
authors: Wang
authors: Department of Physiology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 511436, China.
authors: Jian-Hua
authors: JH
authors: Li
authors: Department of Physiology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 511436, China. Electronic address: tuys@gzhmu.edu.cn.
authors: Yong-Sheng
authors: YS
authors: Tu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid; D002449:Cell Aggregation / Q000187:drug effects; D002452:Cell Count; D004195:Disease Models, Animal; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000473:pathology; D008297:Male; D009336:Necrosis; D019301:Oleic Acid; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007093:Imidazoles; D007211:Indoles; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; C507699:necrostatin-1; D019301:Oleic Acid
keywords: ARDS; Inflammation; Necroptosis; Necrostatin-1