The Mechanism of Adenosine Monophosphate Activated Protein Kinase/Mammalian Target of the Rapamycin Signaling Pathway in the Acute Kidney Injury-Induced Acute Lung Injury
Objective:To investigate the effects of autophagy-related AMPK/mTOR signaling pathway on acute kidney in-jury(AKI)-induced acute lung injury(ALI)and its mechanism.Methods:The 48 male Sprague-Dawley rats were divided into four groups randomly(n=12):(1)sham,(2)ischemia-reperfusion injury(IRI),(3)IRI+rapamycin(RA),and(4)IRI+3-methyladenine(3-MA).Unilateral flank incision was made and right kidney was ligated and excised.The left kidney was subjec-ted to 60 min of ischemia followed by 12,24,48,and 72 h of reperfusion.The levels of Scr,blood urea nitrogen(BUN),lung of Wet/Dry ratio,indexes of inflammation,and oxidative stress were assayed.Histological examinations of lung and kidney were per-formed.The protein expression of AMPK,mTOR,p62,LC3-Ⅱ/LC3-Ⅰ ratio,and Beclin-1,ULK1 was evaluated by western blotting and immunohistochemistry.Results:Compared to the rats from the sham group,IRI rats showed significantly pulmonary dam-age after AKI with increased Scr,BUN,lung of Wet/Dry ratio,indexes of inflammation,and oxidative stress(P＜0.05).The ex-pression of AMPK,LC3-Ⅱ/LC3-Ⅰratio,Beclin-1,and ULK1 and were increased(P＜0.05),while p62 and mTOR were de-creased(P＜0.01).In addition,RA treatment significantly attenuated lung injury by promoting autophagy through the activation of the AMPK/mTOR signaling pathway,and 3-MA treatment exhibited adverse effects inversely.Conclusion:Renal IRI could activate AMPK/mTOR signaling pathway and induce autophagy through this pathway,inhibit inflammatory response,oxidative stress and ap-optosis,thereby significantly alienate AKI and AKI-induced ALI.
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