Regulatory effect of cyclic adenosine monophosphate-protein kinase A signaling pathway on apuaporin 5 expression in a rat model of lung ischemia reperfusion after deep hypothermia and its relation to lung injury

Objective To discuss the regulatory effect of cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signaling pathway on the apuaporin 5 (AQP5) expression in a rat model of lung ischemia reperfusion after deep hypothermia and its relation to lung injury.Methods Twenty-eight Wistar rats were randomly divided into sham group,ischemia-reperfusion group (I/R group),H89 group,and Forskolin group.The left lower hilus pulmonis of L/R group was blocked for 30 min after its body temperature cooled to deep hypothermia and soon opened and rewarmed.The rats in the sham group only undergone thoracotomy without cooling and blocking.The rats in the H89 group and Forskolin group were intraperitoneally injected with H89 and Forskolin 2 days before experiment,respectively.The rest procedures were the same to those in the I/R group.The lung specimens were pathologically observed and wet/dry weight ratio was measured.Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting methods were applied to detect the expression of AQP5 in all groups.Results As compared with sham group,the expression of AQP5 mRNA was reduced (0.67 ± 0.15,P ＜ 0.01),the expression of AQP5 protein declined (0.47 ± 0.09,P ＜ 0.01),W/D ratio increased (5.27 ± 0.92,P ＜ 0.01),the morphology and structure of lung tissue was significandy impaired in the I/R group.As compared with I/R group,the expression of AQP5 mRNA was increased (0.83 ± 0.30,P ＜0.01),the expression of AQP5 protein increased (0.89 ± 0.07,P ＜ 0.01),W/D ratio was reduced (3.98 ± 0.45,P ＜ 0.01),the injury of lung tissue was significantly alleviated in the Forskolin group.There was no statistically significant difference between sham group and Forskolin group.As compared with I/R group and sham group,the AQP5 mRNA expression was decreased (0.53-0.11,P ＜ 0.01),the AQP5 protein expression decreased (0.31 ±0.03,P ＜ 0.0 1),W/D ratio increased (6.13 ±0.78,P ＜ 0.01),and injury of lung tissue was significantly aggravated in H89 group.Conclusion AQP5 was down-regulated in acute lung injury by deep hypothermia ischemia-reperfusion.cAMP-PKA signaling pathway may participate in the regulation of AQP5. Key words: Deep hypothermia; Lung ischemia; Reperfusion injury; Aquaporin 5; Cyclic adenosine monophosphate-protein kinase A signaling pathway