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Sevoflurane Preconditioning Confers Delayed Cardioprotection by Upregulating AMP-Activated Protein Kinase Levels to Restore Autophagic Flux in Ischemia-Reperfusion Rat Hearts.
| Content Provider | Europe PMC |
|---|---|
| Author | Hong, Lei Sun, Ying An, Jian-Zhong Wang, Chen Qiao, Shi-Gang |
| Copyright Year | 2020 |
| Abstract | BackgroundVolatile anesthetic preconditioning confers delayed cardioprotection against ischemia/reperfusion injury (I/R). AMP-activated protein kinase (AMPK) takes part in autophagy activation. Furthermore, autophagic flux is thought to be impaired after I/R. We hypothesized that delayed cardioprotection can restore autophagic flux by activating AMPK.Material/MethodsAll male rat hearts underwent 30-min ischemia and 120-min reperfusion with or without sevoflurane exposure. AMPK inhibitor compound C (250 μg/kg, iv) was given at the reperfusion period. Autophagic flux blocker chloroquine (10 mg/kg, ip) was administrated 1 h before the experiment. Myocardial infarction, nicotinamide adenine dinucleotide (NAD+) content, and cytochrome c were measured. To evaluate autophagic flux, the markers of microtubule-associated protein 1 light chain 3 (LC3) I and II, P62 and Beclin 1, and lysosome-associated membrane protein-2 (LAMP 2) were analyzed.ResultsThe delayed cardioprotection enhanced post-ischemic AMPK activation, reduced infarction, CK-MB level, NAD+ content loss and cytochrome c release, and compound C blocked these effects. Sevoflurane restored impaired autophagic flux through a lower ratio of LC3II/LC3I, downregulation of P62 and Beclin 1, and higher expression in LAMP 2. Consistently, compound C inhibited these changes of autophagy flux. Moreover, chloroquine pretreatment abolished sevoflurane-induced infarct size reduction, CK-MB level, NAD+ content loss, and cytochrome c release, with concomitant increase the ratios of LC3II/LC3I and levels of P62 and Beclin 1, but p-AMPK expression was not downregulated by chloroquine.ConclusionsSevoflurane exerts a delayed cardioprotective effects against myocardial injury in rats by activation of AMPK and restoration of I/R-impaired autophagic flux. |
| ISSN | 12341010 |
| Journal | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| Volume Number | 26 |
| PubMed Central reference number | PMC7288833 |
| PubMed reference number | 32476662 |
| e-ISSN | 16433750 |
| DOI | 10.12659/msm.922176 |
| Language | English |
| Publisher | International Scientific Literature, Inc. |
| Publisher Date | 2020-06-01 |
| Access Restriction | Open |
| Rights License | This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) © Med Sci Monit, 2020 |
| Subject Keyword | AMP-Activated Protein Kinases Autophagy Ischemic Preconditioning, Myocardial Oxidative Stress Reperfusion Injury |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine |
