title: Pharmacological postconditioning with sevoflurane activates PI3K/AKT signaling and attenuates cardiopulmonary bypass-induced lung injury in dog.
abstract: OBJECTIVE
  Sevoflurane, a widely used inhaled anesthetic, showed valid protective effect against ischemia reperfusion injury in lung, however, the underlying molecular mechanisms has yet to be explained.
  
  
  METHODS
  Dogs were divided into four groups: control group, cardiopulmonary bypass (CPB) group, sevoflurane postconditioning group and wortmannin group. Arterial blood was obtained from each group to test the respiratory index and oxygenation index and pulmonary tissues were sampled for apoptotic TUNEL stain. Western Blot was performed to check the level of Akt, p-Akt and nuclear factor kappa B (NF-κB), while ELISA was performed to determine the protein concentrations of tumor necrosis factor α (TNF-α).
  
  
  RESULTS
  Pharmacological postconditioning with sevoflurane protected dog lung from I/R injury with CPB, improved pulmonary dysfunction, and decreased pneumonocyte apoptosis. Application of wortmannin, a specific inhibitor of PI3K, abolished the protective effects and anti-apoptotic effects of sevoflurane-postcondition. Wortmannin also inhibited the sevoflurane-postcondition-induced phosphorylation of AKT and up-regulated the level of NF-κB and TNF-α.
  
  
  CONCLUSIONS
  Accordingly, present study demonstrated that PI3K/AKT/NF-κB pathway plays an important role in the protective effect of sevoflurane postconditioning against CPB induced lung injury.
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Guizhou key laboratory of anesthesia and organ protection, Zunyi Medical College, Zunyi 563000, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China.
authors.forename: Junli
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China.
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Dou
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China. Electronic address: 420557377@qq.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004285:Dogs; D055370:Lung Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D008738:Methyl Ethers / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011183:Postoperative Complications / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D008738:Methyl Ethers; D000077149:Sevoflurane; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Cardiopulmonary bypass; Ischemia-reperfusion injury; Pulmonary; Sevoflurane