title: Activation of necroptosis in a rat model of acute respiratory distress syndrome induced by oleic acid.
abstract: The present study was aimed to investigate the role of necroptosis in the pathogenesis of acute respiratory distress syndrome (ARDS). The rat model of ARDS was induced by intravenous injection of oleic acid (OA), and observed for 4 h. The lung injury was evaluated by arterial blood gas, lung wet-dry weight ratio (W/D) and histological analyses. Simultaneously, bronchoalveolar lavage fluid (BALF) was collected for total and differential cell analysis and total protein determination. Tumor necrosis factor alpha (TNF-α) level in BALF was determined with a rat TNF-α ELISA kit. Expressions of receptor interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL) in lung tissue were determined by Western blot and immunohistochemical staining. The interaction between RIPK1 and RIPK3 was explored by immunoprecipitation. The results showed that, compared with those in control group, total white blood cells count (WBC), polymorphonuclear percentage (PMN%), total protein concentration, TNF-α level in BALF, W/D, and the alveolar-arterial oxygen tension difference (P(A-a)O2) in OA group were significantly increased at 4 h after OA injection. Western blot and immunostaining further showed remarkably increased expressions of RIPK1, RIPK3 and MLKL in lung tissue from OA group. Additionally, immunoprecipitation results indicated an enforced interaction between RIPK1 and RIPK3 in OA group. Collectively, the TNF-α level in BALF and the RIPK1-RIPK3-MLKL signaling pathway in lung tissue were found to be upregulated and activated with the process of ARDS. These findings implicate that RIPK1/RIPK3-mediated necroptosis plays a possible role in the pathogenesis of ARDS, which may provide a new idea to develop novel drugs for the therapy of ARDS.
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 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 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: 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 Physiology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 511436, China.
authors: Jian-Hua
authors: JH
authors: Li
authors: Department of Pathology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 511436, China.
authors: Jie
authors: J
authors: Long
authors: Department of Physiology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 511436, China. tuys@gzhmu.edu.cn.
authors: Yong-Sheng
authors: YS
authors: Tu
mesh_terms: D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D008171:Lung Diseases; D009336:Necrosis; D019301:Oleic Acid; D051381:Rats; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D012120:Respiration Disorders; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha
chemical_list: D014409:Tumor Necrosis Factor-alpha; D019301:Oleic Acid; C119705:RIPK3 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases