title: Propofol protects against hepatic ischemia/reperfusion injury via miR-133a-5p regulating the expression of MAPK6.
abstract: Propofol has been found to play an important role in hepatic ischemia/reperfusion (I/R) injury with the antioxidant effects. However, the molecular mechanism of propofol in hepatic I/R injury has not been fully understood. Male Sprague-Dawley rats were randomly assigned into Sham group, hepatic I/R group, and propofol treatment group. I/R injury was attained by ischemia for 1 h and reperfusion for 2 h. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity were detected. QSG-7701 cells were cultured in hypoxia condition for 15 h and then in reoxygenation condition for 6 h to imitate hypoxia/reoxygenation (H/R) injury in vitro. Real-time RT-PCR and Western blot were performed to determine the expression of miR-133a-5p and MAPK6. Luciferase reporter assay was used to determine the regulation of miR-133a-5p on MAPK6. Propofol significantly reduced the activities of serum AST and ALT induced by hepatic I/R injury in rats. Propofol increased the level of miR-133a-5p and decreased the expression of MAPK6 in vivo and in vitro. Luciferase reporter assay showed that MAPK6 was a target of miR-133a-5p. Knockdown of miR-133a-5p abrogated the effect of propofol on the upregulation of MAPK6 induced by H/R. MAPK6 overexpression promoted the cell apoptosis induced by H/R which could be attenuated by propofol. Finally, we found that miR-133a-5p reversed the protective effect of propofol in rats with hepatic I/R injury. Propofol showed protective roles for hepatic I/R injury in vivo and H/R injury in vitro, which involved with miR-133a-5p regulating the expression of MAPK6.
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hao
authors.affiliation: Department of Anesthesiology, Inner Mongolia Autonomous Region People's Hospital, Huhhot, 010017, China.
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
authors.forename: Qing-Tao
authors.initials: QT
authors.lastname: Meng
authors.affiliation: Department of Anesthesiology, Inner Mongolia Autonomous Region People's Hospital, Huhhot, 010017, China.
authors.forename: Mu-Er
authors.initials: ME
authors.lastname: Tie
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
authors.forename: Shao-Qing
authors.initials: SQ
authors.lastname: Lei
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
authors.forename: Zhong-Yuan
authors.initials: ZY
authors.lastname: Xia
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology / Q000627:therapeutic use*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*
chemical_list: C548234:MIRN133 microRNA, human; C549446:MIRN133 microRNA, rat; D035683:MicroRNAs; D020011:Protective Agents; D020928:Mitogen-Activated Protein Kinases; D010100:Oxygen; D015742:Propofol
keywords: alanine aminotransferase; cell apoptosis; hepatic I/R injury; hypoxia/reoxygenation; miR-133a; propofol