title: Sevoflurane protects against hepatic ischemia/reperfusion injury by modulating microRNA-200c regulation in mice.
abstract: This present study was aimed to investigate the molecular mechanisms involved in sevoflurane protection of hepatic ischemia-reperfusion (I/R) injury. Firstly, we investigated the protective effects of sevoflurane against hepatic I/R injury. Biochemical analysis results showed that sevoflurane preconditioning significantly protected against hepatic I/R injury by reducing liver enzymes and improving antioxidant defense markers. We also found that sevoflurane attenuates I/R-induced hepatic cell death, by TUNEL staining, DNA fragmentation ELISA and PARP activity determination. Next, In order to find the molecular mechanism of sevoflurane preconditioning in hepatic I/R injury, we poured our attention to microRNAs regulation. We focused on miR-200c, one of microRNAs which screened from the gene expression omnibus (GEO). Furthermore, a hydrogen peroxide (H2O2)-induced oxidative stress apoptosis model was also established to mimic hepatic I/R injury, the effects of MiR-200c was investigated. We observed that MiR-200c inhibition decreased the H2O2-induced apoptosis of hepatic AML-12 cells. And also, ZEB1 is found as a target gene of miR-200c and is involved in H2O2-induced apoptosis. On the other hand, the in vivo model was established to examine whether sevoflurane protect against hepatic IR injury by downregulating MiR-200c. Together with the biochemical tests and apoptosis detection, results showed that over-expression of miR-200c significantly inhibited the protect effect of sevoflurane in Hepatic IR injury. Summarizing, sevoflurane preconditioning seems to ameliorate hepatic I/R injury in mice, mediated by mechanisms that include microRNA 200c down regulation. However, further more studies need to be carried out to verify this point.
authors: Department of Anesthesiology, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu 215000, China.
authors: Yamou
authors: Y
authors: Wu
authors: Department of Anesthesiology, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu 215000, China. Electronic address: gu_chengyong@126.com.
authors: Chengyong
authors: C
authors: Gu
authors: Department of Anesthesiology, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu 215000, China.
authors: Xiaochen
authors: X
authors: Huang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006861:Hydrogen Peroxide / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008738:Methyl Ethers; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; C519422:ZEB1 protein, mouse; D000071799:Zinc Finger E-box-Binding Homeobox 1; D000077149:Sevoflurane; D006861:Hydrogen Peroxide
keywords: Apoptosis; Hepatic IR injury; ROS; Sevoflurane; ZEB1; miR-200c