The Protective Effects Of Ischemic Postconditioning On Lung Ischemic Reperfusion Injury In Rats Via PI3K/Akt Pathway

Objective To investigate the protective effects of ischemic postconditioning on lung ischemic reperfusion injury in rats via PI3K/Akt pathway.Methods Twenty-four SD rats were randomly divided into3groups, sham-operated group (S), ischemic-reperfusion group (I/R) and ischemic postconditioning group (IpostC). There were8rats in each group. All the rats received left thoracotomy after anesthesia. In the sham-operated group, a line was only placed around the left hilum but not fastened. In the ischemic-reperfusion group, a line was fastened to block the blood flow of the left lung for30minutes, then loosened for reperfusion for120minutes. In the ischemic postconditioning group, after blocking the blood flow of the left lung for30minutes, the left hilum was occluded for30seconds and loosened for30seconds (repeating3cycles for3minute), then the line was loosened for120minutes. Akt, p-Akt, p70S6K, p-p70S6K, mTOR, p-mTOR, LC3-II protein expression were tested by Western blotting. Apoptotic cells were tested by TUNEL, wet to dry weight ratio(W/D)in lung tissue was determined respectively. Histopathological changes of lung tissues were observed through light microscope. Lung injury scores was calculated, autophagic vacuoles were determined by electron microscope.Results The expression of Akt was0.57±0.04in group S,0.48±0.09in group I/R,0.61±0.04in group IpostC. The expression of p-Akt was0.20±0.04in group S,0.29±0.08in group I/R,0.58±0.11in group IpostC. The expression of p70S6K was0.55±0.03in group S,0.52±0.04in group I/R,0.63±0.05in group IpostC. The expression of p-p70S6K was0.22±0.10in group S,0.27±0.07in group I/R,0.50±0.13in group IpostC. The expression of mTOR was0.37±0.07in group S,0.40±0.03in group I/R,0.46±0.09in group IpostC. The expression of p-mTOR was0.31±0.10in group S,0.33±0.09in group I/R,0.55±0.07in group IpostC. The expression of LC3-Ⅱ was0.25±0.06in group S,0.53±0.08in group I/R,0.38±0.03in group IpostC. An apoptotic index was7.63±2.41in group S,18.43±2.39in group I/R,12.78±3.25in group IpostC. W/D was4.77±0.14in group S,6.20±0.50in group I/R,5.28±0.37in group IpostC. Lung injury scores was5.58±0.39in group S,15.79±1.33in group I/R,11.67±1.55in group IpostC. Compared with sham-operated group, the expression of mTOR and p-mTOR were no significantance differ in ischemic-reperfusion group (P>0.05), but increased in ischemic postconditioning group (P<0.05). LC3-II, apoptotic index, W/D and lung injury score in lung tissue markedly increased in ischemic-reperfusion and ischemic postconditioning group (P<0.05). Compared with ischemic-reperfusion group, the expression of Akt, p-Akt, p70s6K, p-p70s6K, mTOR, p-mTOR was markedly increased in ischemic postconditioning group respectively (P<0.05), while the expression of LC3-II, apoptotic index, W/D and lung injury score reduced significantly (P<0.05).Conclusion Ischemic postconditioning has a protective effect on lung ischemic reperfusion injury by reduce autophagy and apoptotic through the activation of PI3K/Akt signaling pathway and downstream protein.