Effect of GSK-3β inhibitor TDZD-8 on activation of NF-κB during lung ischemia-reperfusion in rats / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effect of GSK-3β inhibitor TDZD-8 on activation of NF-κB during lung ischemia-reperfusion (I/R) in rats.Methods Thirty-two healthy male Sprague-Dawley rats,aged 8-10 weeks,weighing 250-280 g,were randomly divided into 4 groups (n=8 each) sham operation group (sham group) ; I/R group,I/R + dimethyl sulfoxide (DMSO) group and I/R + TDZD-8 group.Lung I/R was induced by clamping the left hilum of lung for 1 h followed by 2 h reperfusion.10％ DMSO and TDZD-8 1 mg/kg were injected intravenously at 5 min betore reperfusion in groups I/R + DMSO and I/R + TDZD-8,respectively.Blood samples were taken at 2 h of reperfusion for determination of arterial partial pressure of oxygen (PaO2) and concentrations of plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).The animals were then sacrificed and the left lung was removed for determination of W/D lung weight ratio,myeloperpxidase (MPO) activity,expression of phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β) and phosphorylated nuclear factor-kappa B p65 (pNF-κB p65) and for microscopic examination.Results Compared with sham group,PaO2 and the expression of pGSK-3β were significantly decreased,and the concentrations of plasma IL-6 and TNF-α,W/D lung weight ratio,MPO activity and expression of p-NF-κB p65 were significantly increased in the other groups (P ＜ 0.05),and PaO2 and the expression of p-GSK-3β were significantly increased and the other parameters were significantly decreased in I/R+ TDZD-8 group (P＜ 0.05).There were no significant differences in the parameters mentioned above among groups I/R and I/R + DMSO (P ＞ 0.05).Microscopic examination showed that I/R-induced lung injury was ameliorated by TDZD-8.Conclusion GSK-3β inhibitor TDZD-8 can attenuate lung I/R injury by downregulating phosphorylation of NF-κB p65 and inhibiting inflammatory response.