科研之友
微信
新浪微博
Facebook
分享链接
摘要
Sevoflurane preconditioning has shown to exert delayed caridioprotection against subsequent ischemia and reperfusion injury, but the mechanisms underlying is unclear. Inhibition of autophagy by 3-methyladenine (3-MA) or knockdown of Beclin 1 leads to enhanced cardiac myocyte survival. Our study aimed to test whether sevoflurane preconditioning provides a second window of anesthetic preconditioning (SWOP) via inhibit Beclin 1-mediated autophagic cell death. H9c2 rat cardiomyocytes were randomly divided into five groups: Control (CON) group; hypoxia/reoxygenation (H/R) group, rat cardiomyocytes was exposed in the airtight container for 2 h followed by 1 h of reoxgenation; SWOP group, rat cardiomyocytes was exposed to 1 h of 2.5% sevoflurane 24 h before H/R; Autophagic inhibitors, 3-methyladenine (3-MA, 10 mM) was added to culture medium 15 min before sevoflurane exposure (3-MA+SWOP group) or cells were treated by 3-MA alone (3-MA group). The cell proliferation was significantly increased in SWOP group (79.49 +/- 1.37%, P < 0.05) when compared to H/R group (62.2 +/- 6.49%, P < 0.05). 3-MA administered before SWOP significantly attenuated the H/R induced autophagy and cell death. H/R injury up-regulated the expression of LC3-II and Beclin 1 proteins (342 +/- 66% and 163 +/- 18%, respectively, P < 0.05) compared to the CON group (100%), which were increased in SWOP group (202 +/- 77% and 128 +/- 8%, respectively, P < 0.05). The expression of LC3-II and Beclin 1 proteins was decreased in 3-MA group (110 +/- 28% and 97 +/- 6%, respectively) and 3-MA+ SWOP group (93 +/- 7% and 98 +/- 6%, respectively) compared with H/R group, but Bcl-2 was upregulated in 3-MA group (158 +/- 4%) and 3-MA+ SWOP group (156 +/- 5%) compared to H/R group (103 +/- 7%). In conclusion, sevoflurane preconditioning confers delayed cardioprotection via inhibition Beclin 1-mediated autophagic cell death in cardiac myocytes 24 h before exposed to H/R injury.
