Effect of cardamonin on acute lung injury induced by hemorrhagic shock and resuscitation in rats

Abstract

Objective To evaluate the effect of cardamonin on acute lung injury induced by hemorrhagic shock and resuscitation (HSR) in rats. Methods Thirty-two male Sprague-Dawley rats, aged 18-24 weeks, weighing 200-250 g, were divided into 4 groups (n = 8 each) using a random number table: sham operation group (group Sham); group HSR; cardamonin group (group CA); cardamonin + adenosina A2A receptor antagonist ZM241385 group (group CZM). Bilateral common carotid arteries were only cannulated in group Sham.The left common carotid artery was cannulated for blood-letting until mean arterial pressure was reduced to 35-45 mmHg and maintained at this level for 30 min, and the animals were then resuscitated by infusion of shed blood and normal saline two-fold volume of shed blood to establish HSR model in HSR, CA and CZM groups.ZM241385 5 mg/kg was injected intraperitoneally at 30 min before blood-letting in group CZM, and cardamonin 75 mg/kg was injected intraperitoneally immediately after the beginning of resuscitation in CA and CZM groups.The rats were sacrificed at 2 h after completion of resuscitation, bronchoalveolar lavage fluid (BALF) was collected for determination of neutrophil count, and lungs were removed for microscopic examination of the pathological changes and for determination of wet/dry lung weight ratio (W/D ratio), contents of tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay) and expression of adenosine A2A receptors in lung tissues (by Western blot). Results Compared with group Sham, the neutrophil count in BALF, W/D ratio and contents of TNF-α, IL-1β and IL-6 were significantly increased, the expression of adenosine A2A receptors was significantly down-regulated in group HSR, and the neutrophil count in BALF and contents of TNF-α and IL-6 were significantly increased (P 0.05). Compared with group HSR, the neutrophil count in BALF, W/D ratio and contents of TNF-α, IL-1β and IL-6 were significantly decreased, the expression of adenosine A2A receptors was significantly up-regulated (P 0.05). Compared with group CA, the neutrophil count in BALF, W/D ratio and contents of TNF-α, IL-1β and IL-6 were significantly increased, the expression of adenosine A2A receptors was significantly down-regulated (P<0.05), and the pathological changes were aggravated in group CZM. Conclusion Cardamonin can attenuate acute lung injury induced by HSR in rats, and activated adenosine A2A receptors and inhibited inflammatory responses are involved in the mechanism. Key words: AMOMUM COSTATUM; Shock, hemorrhagic; Respiratory distress syndrome, adult