title: Dexmedetomidine protects against lung ischemia-reperfusion injury by the PI3K/Akt/HIF-1α signaling pathway.
abstract: To evaluate the role of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/hypoxia-inducible factor 1α (HIF-1α) signaling pathway in the protection by dexmedetomidine against lung ischemia-reperfusion injury (IRI) in rats.
  
  
  
  Forty-eight male Sprague-Dawley rats weighing 250-350 g were randomly divided into six groups (n = 8 each group): sham group, IRI group, low-dose dexmedetomidine group (LD group), high-dose dexmedetomidine group (HD group), combined low-dose dexmedetomidine and LY294002 group (LDL group), and combined high-dose dexmedetomidine and LY294002 group (HDL group). A 30-min ischemia was induced by occluding the hilum of the left lung, followed by a 120-min reperfusion by removing occlusion of the hilum. After the left lung was removed, the wet/dry weight ratio (W/D) of the lung tissues was determined. Pathological changes of lung tissues were evaluated by light and electron microscopes and the expression of p-Akt and HIF-1α in the lung tissues was determined by western blotting.
  
  
  
  Compared with the sham group, both the W/D ratio and lung injury were significantly increased, the p-Akt expression was down-regulated and HIF-1α expression was up-regulated in the five experimental groups. Compared with the LD and LDL groups, both the W/D ratio and lung injury were decreased, but the expression of p-Akt and HIF-1α was increased in the HD and HDL groups.
  
  
  
  Administration of dexmedetomidine before ischemia can provide a protection against lung IRI by re-installing the PI3K/Akt/HIF-1α signaling pathway.
authors.affiliation: Department of Anesthesiology, Henan Provincial People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Henan Provincial People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China. mazuizhang@163.com.
authors.forename: Jia-Qiang
authors.initials: JQ
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Henan Provincial People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Fan-Min
authors.initials: FM
authors.lastname: Meng
authors.affiliation: Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. xuefushan@aliyun.com.
authors.forename: Fu-Shan
authors.initials: FS
authors.lastname: Xue
mesh_terms: D000818:Animals; D002867:Chromones / Q000494:pharmacology; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000627:therapeutic use*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects; D007511:Ischemia / Q000150:complications*; D055370:Lung Injury; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D006993:Hypnotics and Sedatives; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D020927:Dexmedetomidine; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt
keywords: Dexmedetomidine; Hypoxia-inducible factor 1α; Ischemia–reperfusion injury; Lung; Phosphoinositide-3-kinase