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Role of Nuclear Factor-κB-induced Autophagy in Delayed Cardioprotection of Sevoflurane Preconditioning

Author: QiaoShiGang
Tutor: WangZuo；XieHong
School: Suzhou University
Course: Anesthesiology
Keywords: Anesthetic, Inhalation Myocardial reperfusion injury NF-kappa B Autophagy Lysosomes
CLC: R965
Type: Master's thesis
Year: 2010
Downloads: 156
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Abstract


Aims To investigate the mechanism of Nuclear Factor-кB-induced autophagy in delayed cardioprotection of sevoflurane preconditioning against myocardial ischemia /reperfusion (I/R) injury in rats in vivo.Methods In the study, we set up the model of myocardial I/R in vivo, evaluated the effect of sevoflurane preconditioning with measuring myocardial infarct size. The tissue injury of myocardium was examined with optical microscope, autophagosomes and lysosomes were observed with transmission electron microscopy (TEM). To examine the involvement of NF-κB and autophagy in sevoflurane preconditioning, the specific inhibitor parthenolide (PTN) was injected intraperitoneally in rats, proteins related to NF-κB and autophagy were determined with electrophoretic mobility shift assay and Western blot.Results Preconditioning with sevoflurane reduced myocardial infarct size in rats as compared with the single ischemia reperfusion group, and the tissue injury also decreased. Autopagosomes were detected in sevoflurance preconditioning groups by TEM before ischemia. NF-кB-DNA binding activity and the levels of TNF-α, IL-1β, LC3-Ⅱ, and Cathepsin B were all significantly up-regulated in sevoflurane preconditioning group before ischemia in rat myocardium, at the end of reperfusion they were all up-regulated compared to the control gtoup, but the extent of the sevoflurane preconditioning group was lower than the single ischemia reperfusion group except the Cathepsin B, and this was blocked by using PTN.Conclusions Sevoflurane preconditioning activated NF-κB and subsequent up-regulated of TNF-α, IL-1βand autophagy expression before ischemia inhibited the excessive activation of NF-κB and autophagy at the end of reperfusion, the results of this study indicated that attenuation of autophagic cell death was one of important roles in the delayed cardioprotective mechanism of sevoflurane preconditioning.

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