Effect of cuecumin on mammalian target of rapamyein signaling pathway during ischemia-reperfusion injury in isolated rat lungs / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of curcumin on the mammalian target of rapamyein (mTOR) signaling pathway during ischemia-reperfusion (I/R) injury in isolated rat lungs.Methods Sixty-four clean-grade healthy male Sprague-Dawley rats,aged 3-4 months,weighing 250-320 g,were divided into 4 groups (n=16 each) using a random number table method:sham operation group (S group),I/R group,low-dose curcumin group (LC group) and high-dose curcumin group (HC group).The rats only received in vitro perfusion without ischemia in S group.Isolated rat lungs were subjected to 60 min of ischemia followed by 75-min reperfusion to establish the lung I/R injury model in I/R group.Curcumin 5 and 10 μmol/L were added to perfusion fluid from the beginning of reperfusion in LC and HC groups,respectively.Airway resistance (Res),lung compliance,perfusion flow (Flow) and pulmonary venous partial pressure of oxygen (PaO2) were recorded at 10 min of first perfusion (T0) and 15,45 and 75 min of reperfusion (T1-3).Wet/dry lung weight ratio (W/D ratio) was measured at the end of reperfusion.The morphological structure and ultrastructure of lung tissues were observed by using a light microscope and a transmission electron microscope,respectively.The expression of mTOR,Tau protein,nuclear factor kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α) mRNA in lung tissues was detected by real-time polymerase chain reaction.The expression of mTOR,phosphorylated Tau protein (pS396 Tau protein),NF-κB and TNF-α protein in lung tissues was determined by Western blot.Results Compared with S group,Res at T1-3 and W/D ratio at T3 were significantly increased,lung compliance,Flow and PaO2 were decreased at T1-3,and the expression of mTOR,NF-κB and TNF-α protein and mRNA,Tau protein mRNA and pS396 Tau protein was up-regulated at T3 in I/R,LC and HC groups (P＜0.05).Compared with I/R group,Res at T1-3 and W/D ratio at T3 were significantly decreased,lung compliance,Flow and PaO2 were increased at T1-3,and the expression of mTOR,NF-κB and TNF-α protein and mRNA,Tau protein mRNA and pS396 Tau protein was down-regulated at T3 in LC and HC groups (P＜0.05).Compared with LC group,Res at T1-3 and W/D ratio at T3 were significantly decreased,lung compliance,Flow and PaO2 were increased at T1-3,and the expression of mTOR,NF-κB and TNF-α protein and mRNA,Tau protein mRNA and pS396 Tau protein was down-regulated at T3 in HC group (P＜0.05).The microscopic examination showed that the injury to lung tissues was significantly attenuated in LC and HC groups as compared with I/R group.Conclusion The mechanism by which curcumin reduces I/R injury in isolated rat lungs is related to inhibiting mTOR signaling pathway.