摘要Aim: The activation of extracellular signal-regulated kinase (ERK)1/2 protects against ischemic-reperfusion injury. Whether ERK1/2 mediates the cardioprotection of sevoflurane postconditioning is unknown. We tested whether sevoflurane postconditioning produces cardioprotection via an ERKl/2-depen- dent mechanism. Methods: In protocol 1, Langendorff-perfused Sprague-Dawley rat hearts (n=84, 12 per group), with the exception of the Sham group, were sub- jected to 30 min ischemia followed by 90 min reperfusion and were assigned to the untreated (control) group, followed by 4 cycles of ischemic postconditioning (25 s of each), 3% (v/v) sevoflurane postconditioning (for 5 rain and 10 min of washout), and the PD98059 solvent DMSO (<0.2%), ERK1/2 inhibitor PD98059 (20 μmol/L), and Sevo+PD administration. Left ventricular hemodynamics and coronary flow at 30 min of equilibrium were recorded at 30, 60, and 90 rain of repeffusion, respectively. Acute infarct size was measured by triphenyltetra- zolium chloride staining. The configuration of mitochondria was observed by an electron microscope. Western blot analysis was used to determine the contents of cytosolic and mitochondrial cytochrome c at the end of reperfusion. In pro- tocol 2, after 15 rain of reperfusion, the expression of total and phosphorylated forms of ERK1/2 and its downstream target p70S6K was determined by West- ern blotting. Results: No differences in baseline hemodynamics were observed among the experimental groups (P>0.05). After reperfusion, compared with the control group, sevoflurane postconditioning and ischemic postconditioning sig- nificantly (P<0.05) improved functional recovery and largely (P<0.05) de- creased myocardial infarct size (22.9%±4.6% and 21.2%±3.8%, vs 39.4%± 5.7%, both P<0.05). Sevoflurane-mediated protection was abolished by PD98059. Conclusion: Anesthetic postconditioning by sevoflurane effectively protects against reperfusion damage by activating ERK1/2 in vitro.