| Popis: |
Cannabinoid receptor-2 activation plays a protective role against ischemic reperfusion injury (IRI) in various organs, and exerts a protective effect against paraquat-induced acute lung injury, while the role of CB(2) in lung IRI remains unclear. Hence, the present study was designed to explore the role of CB(2) in lung IRI, and whether the PI3K pathway was involved. C57BL/6 mice were subjected to lung ischemia by clamping the left hilum for 1 hour, followed by 2 hours’ reperfusion. Mice were pretreated with vehicle, CB(2) agonist JWH133, or antagonist AM630 followed by JWH133. Arterial blood and left lung tissues were collected to detect the PaO(2)/FiO(2) ratio, lung wet-to-dry weight ratio, lung pathologic scoring, pro-inflammatory cytokines, MDA, and SOD. Secondly, mice were pretreated with vehicle, JWH133, or both PI3K-inhibitor LY294002 and JWH133. Arterial blood and left lung tissues were collected for the above studies and protein expression of CB(2) receptor, p-AKT, and AKT. After mice were pretreated with JWH133, IR-induced lung edema and lung histopathologic changes were significantly attenuated. Pretreatment with JWH133 improved PaO(2)/FiO(2) ratio, decreased lung TNF-α, IL-6, MDA levels and MPO activities, and increased SOD activity. By contrast, the protective effect of JWH133 was blocked by pretreatment with CB(2) antagonist AM630. Similarly, pretreatment with PI3K-inhibitor weakened the protection induced by JWH133, and downregulated the expression of p-AKT without altering CB(2) expression. The study suggested that activation of CB(2) receptor plays a protective role against IR-induced lung injury through reducing inflammation in mice. The PI3K/Akt pathway might be involved in the protective effect of CB(2) receptors in lung IRI. |
