Effect of sevoflurane postconditioning on expression of Pim-1 kinase during myocardial ischemia-reperfusion in rats: an in vitro experiment

Objective To evaluate the effect of sevoflurane postconditioning on the expression of Pim-1 kinase during myocardial ischemia-reperfusion(I/R)in rats. Methods Male Sprague-Dawley rats, weighing 250-300 g, were used in this study.After the animals were anesthetized, their hearts were immediately removed and retrogradely perfused with an oxygenated K-H solution at 37 ℃ in a Langendorff apparatus.Thirty-six isolated rat hearts were assigned into 3 groups(n=12 each)using a random number table: control group(group C), group I/R and sevoflurane postconditioning group(group SP). The hearts were subjected to ischemia for 30 min followed by 120 min of reperfusion to establish the model of myocardial I/R injury.In group SP, the hearts were perfused with K-H solution saturated with 3% sevoflurane for 15 min starting from the beginning of reperfusion.Heart rate(HR), left ventricular end-diastolic pressure(LVEDP), left ventricular developed pressure(LVDP)and the maximum rate of increase and decrease of left ventricular pressure(±dp/dtmax) were recorded at the end of equilibration and 30, 60, 90 and 120 min of reperfusion.Myocardial tissues were obtained at T2 for determination of the expression of Pim-1 kinase, Bcl-2 and cytochrome c(Cyt c)in cytoplasm and mitochondria by Western blot.The hearts were selected at T4 for determination of myocardial infarct size(by TTC staining)and for examination of mitochondrial ultrastructure(with transmission electron microscope). Results Compared with group C, HR, LVDP and ±dp/dtmax were significantly decreased, and LVEDP was increased at T1-4, the myocardial infarct size was enlarged, the expression of Pim-1 and Bcl-2 in cytoplasm and mitochondria was down-regulated, the expression of Cyt c in cytoplasm was up-regulated, and the expression of Cyt c in mitochondria was down-regulated in group I/R(P<0.05). Compared with group I/R, HR, LVDP and ±dp/dtmax were significantly increased, and LVEDP was decreased at T1-4, the myocardial infarct size was decreased, the expression of Pim-1 kinase and Bcl-2 in cytoplasm and mitochondria was up-regulated, the expression of Cyt c in cytoplasm was down-regulated, and the expression of Cyt c in mitochondria was up-regulated in group SP(P<0.05). The damage to mitochondria was significantly attenuated in group SP as compared with group I/R, and was aggravated as compared with group C. Conclusion The mechanism by which sevoflurane postconditioning attenuates myocardial I/R may be related to up-regulation of Pim-1 kinase expression in rats. Key words: Proto-oncogene proteins; Anesthetics, inhalation; Ischemic postconditioning; Myocardial reperfusion injury