Abstract: Objective To investigate the influences of isoflurane on high glucose-induced cardiomyocyte injury in H9C2 cells and its mechanism through phosphatidylinositol 3 kinase (PI3K) / protein kinase B (AKT) / mammalian target of rapamycin (mTOR) signaling pathway. Methods H9C2 cardiomyocytes in the logarithmic growth phase were selected and grouped into 5 groups: control group ( untreated H9C2 cardiomyocytes), high glucose group (35 mmol / L glucose), isoflurane low-dose group (35 mmol / L glucose + 1 % isoflurane), isoflurane high-dose group (35 mmol / L glucose + 2 % isoflurane), isoflurane + LY294002 group (35 mmol / L glucose + 2 % isoflurane + 50 μmol / L LY294002). The proliferation of cells in each group was detected by CCK-8 method. The autophagy of cells in each group was observed by transmission electron microscope. The apoptosis of cells in each group was detected by flow cytometry. The expression levels of Beclin1, Bax, and PI3K/ Akt / mTOR pathway related proteins in the cells of each group were measured by Western blotting. Results The autophagosomes formed in the cells of the high glucose group could be observed obviously. The proliferation rate, and the levels of p-PI3K/ PI3K, p-Akt / Akt, and p-mTOR/ mTOR in high glucose group were decreased, while the apoptosis rate, and the expression levels of Bax and Beclin1 proteins were increased significantly when compared with those in the control group (P< 0. 05). After treated with different concentrations of isoflurane, the cell proliferation rate, and the levels of p-PI3K/ PI3K, p-Akt / Akt and p-mTOR/ mTOR were increased significantly, while the numbers of autophagosomes, the apoptosis rate, and expression levels of Bax and Beclin1 proteins were decreased significantly when compared with those in the high glucose group (P < 0. 05). The cell proliferation rate, levels of p-PI3K/ PI3K, p-Akt / Akt and p-mTOR/ mTOR decreased in the isoflurane + LY294002 group when compared with those in the isoflurane high-dose group, while the number of autophagosomes, the apoptosis rate, and the expression levels of Bax and Beclin1 proteins were increased significantly (P < 0. 05). Conclusion Isoflurane can inhibit the high-glucose induced autophagy and apoptosis in the H9C2 cardiomyocytes, which improves cell survival rate and reduces cell injury. The underlying mechanism may be related to the activation of PI3K/ Akt / mTOR pathway.

Key words: isoflurane, PI3K/ Akt / mTOR pathway, high glucose, apoptosis, autophagy, cardiomyocyte injury