Sevoflurane postconditioning reduces myocardial reperfusion injury in rat isolated hearts via activation of PI3K/Akt signaling and modulation of Bcl-2 family proteins |
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| Authors: | Li-na Yu Jing Yu Feng-jiang Zhang Mei-juan Yang Ting-ting Ding Jun-kuan Wang Wei He Tao Fang Gang Chen and Min Yan |
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| Institution: | (1) Department of Anesthesiology, Fuwai Cardiovascular Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, 100037 Beijing, China;(2) Department of Cardiovascular Surgery and Cardiovascular Institute, General Hospital of the People’s Liberation Army, 100853 Beijing, China;(3) No. 167 Beilishi Road, 100037 Xicheng District, Beijing, China; |
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| Abstract: | Sevoflurane postconditioning reduces myocardial infarct size. The objective of this study was to examine the role of the phosphatidylinositol-3-kinase
(PI3K)/Akt pathway in anesthetic postconditioning and to determine whether PI3K/Akt signaling modulates the expression of
pro- and antiapoptotic proteins in sevoflurane postconditioning. Isolated and perfused rat hearts were prepared first, and
then randomly assigned to the following groups: Sham-operation (Sham), ischemia/reperfusion (Con), sevoflurane postconditioning
(SPC), Sham plus 100 nmol/L wortmannin (Sham+Wort), Con+Wort, SPC+Wort, and Con+dimethylsulphoxide (DMSO). Sevoflurane postconditioning
was induced by administration of sevoflurane (2.5%, v/v) for 10 min from the onset of reperfusion. Left ventricular developed
pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximum increase in rate of LVDP (+dP/dt), maximum decrease in rate of LVDP (−dP/dt), heart rate (HR), and coronary flow (CF) were measured at baseline, R30 min (30 min of reperfusion), R60 min, R90 min, and
R120 min. Creatine kinase (CK) and lactate dehydrogenase (LDH) were measured after 5 min and 10 min reperfusion. Infarct size
was determined by triphenyltetrazolium chloride staining at the end of reperfusion. Total Akt and phosphorylated Akt (phospho-Akt),
Bax, Bcl-2, Bad, and phospho-Bad were determined by Western blot analysis. Analysis of variance (ANOVA) and Student-Newman-Keuls’
test were used to investigate the significance of differences between groups. The LVDP, ±dP/dt, and CF were higher and LVEDP was lower in the SPC group than in the Con group at all points of reperfusion (P<0.05). The SPC group had significantly reduced CK and LDH release and decreased infarct size compared with the Con group
(22.9±8)% vs. (42.4±9.4)%, respectively; P<0.05]. The SPC group also had increased the expression of phospho-Akt, Bcl-2, and phospho-Bad, and decreased the expression
of Bax. Wortmannin abolished the cardioprotection of sevoflurane postconditioning. Sevoflurane postconditioning may protect
the isolated rat heart. Activation of PI3K and modulation of the expression of pro- and antiapoptotic proteins may play an
important role in sevoflurane-induced myocardial protection. |
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| Keywords: | Sevoflurane Postconditioning Cardioprotection Akt Bcl-2 Bad |
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