Role of PI3K∕Akt signaling pathway in dexmedetomidine-induced reduction of lung ischemia-reper-fusion injury in rats undergoing cardiopulmonary bypass / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of PI3K∕Akt signaling pathway in dexmedetomidine-in-duced reduction of lung ischemia-reperfusion ( I∕R ) injury in rats undergoing cardiopulmonary bypass (CPB). Methods Twenty-four healthy adult male Sprague-Dawley rats, weighing 350-450 g, were di-vided into 3 groups (n＝8 each) using a random number table method: group I∕R, dexmedetomidine group ( group D) and dexmedetomidine plus wortmannin group (group D+W). Rats were anesthetized with pento-barbital sodium. Lung I∕R was induced by clamping the left hilum of lung for 60 min starting from 10 min of CPB, followed by 120-min reperfusion. Dexmedetomidine was injected via the tail vein in a dose of 3 μg∕kg at 10 min before clamping the left hilum of lung, followed by a continuous infusion of 1. 5 μg·kg-1·h-1 until the end of CPB in group D. Dexmedetomidine was injected via the tail vein in a dose of 3 μg∕kg at 10 min before clamping the left hilum of lung, followed by a continuous infusion of 1. 5 μg·kg-1·h-1until the end of CPB, and wortmannin was simultaneously injected via the tail vein in a dose of 15 μg∕kg, fol-lowed by a continuous infusion of 2. 0 μg·kg-1·min-1until the end of CPB in group D+W. Arterial blood samples were collected immediately before CPB ( T1), immediately after opening the left hilum of lung (T2) and at 1. 5 h after the end of CPB (T3), and oxygenation index (OI) and respiratory index (RI) were calculated. The rats were sacrificed at T3, and the left lung was removed for examination of the patho-logical changes which were scored and for determination of apoptosis rate ( by flow cytometry) and Akt, Bad, activated caspase-3, phosphorylated Akt ( p-Akt) and phosphorylated Bad ( p-Bad) in lung tissues ( by Western blot). Results Compared with the baseline at T1, OI was significantly decreased and RI was increased at T2and T3in the three groups (P＜0. 05). OI was significantly decreased and RI was increased at T3than at T2in the three groups ( P＜0. 05). Compared with group I∕R, OI was significantly increased and RI was decreased at T3, the pathological damage score and apoptosis rate were decreased, ratios of p-Akt∕Akt and p-Bad∕Bad were increased, and the expression of activated caspase-3 was down-regulated in group D, and OI was significantly decreased and RI was increased at T2in group D+W ( P＜0. 05). Com-pared with group D, OI was significantly decreased and RI was increased at T3, the pathological damage score and apoptosis rate were increased, ratios of p-Akt∕Akt and p-Bad∕Bad were decreased, and the ex-pression of activated caspase-3 was up-regulated in group D+W ( P＜0. 05). Conclusion Dexmedetomi-dine can reduce dexmedetomidine-induced reduction of lung I∕R injury through activating PI3K∕Akt signa-ling pathway and inhibiting cell apoptosis in rats undergoing CPB.