科研之友
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摘要
Background Opioid preconditioning (PC) reduces anoxia/reoxygenation (A/R) injury to various cells. However, it remains unclear whether opioid-incluced delayed PC would show anti-apoptotic effects on pulmonary artery endothelial cells (PAECs) suffering from A/R injury. The present study was conducted to elucidate this issue and to investigate the potential mechanism of opioid-incluced delayed PC. Methods Cultured porcine PAECs underwent 16-hour anoxia followed by 1-hour reoxygenation 24 hours after pretreatment with saline (NaCl; 0.9%) or morphine (1 mu mol/L). To determine the underlying mechanism, a non-selective K(ATP) channel inhibitor glibenclamide (Glib; 10 mu mol/L), a nitric oxide (NO) synthase blocker NG-nitro-L-arginine methyl ester (L-NAME; 100 mu mol/L), and an opioid receptor antagonist naloxone (Nal; 10 mu mol/L) were given 30 minutes before the A/R load. The percentage of apoptotic cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. eNOS mRNA level was measured by real-time polymerase chain reaction (PCR). NO content of PAECs supernatants was measured with the Griess reagent. Results Compared to the A/R PAECs, morphine-induced delayed PC significantly reduced PAECs apoptosis ((18.1 +/- 1.9)% vs (5.5 +/- 0.3)%; P < 0.05), increased NO release ((11.4 +/- 1.3) mu mol/L vs (20.5 +/- 2.1) mu mol/L, P < 0.05), and up-regulated eNOS gene expression nearly 9 times (P < 0.05). The anti-apoptosis effect of morphine was abolished by pretreatment with Glib, L-NAME and Nal, but the three agent-selves did not aggravate the A/R injury. Furthermore, L-NAME and Nal offset the enhanced release of NO caused by pretreatment with morphine. Conclusions Morphine-induced delayed PC prevents A/R injury of PAECs. This effect may be mediated by activation of KATP channel via opioid receptor and NO signaling pathways.
- 出版日期2008-7-20
- 单位哈尔滨医科大学
