Role of Toll-like receptor 4 in non-medullary and medullary cells in lung ischemia-reperfusion injury in mice / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of Toll-like receptor 4 (TLR4) in non-medullary andmedullary cells in lung ischemia-reperfusion (I/R) injury in mice.Methods Ten healthy male TLR4+/+ in non-medullary cells/TLR4+/+ in medullary cells (WT/WT) mice,10 TLR4-/-in non-medullary cells/ TLR4-/-in medullary cells (KO/KO) homozygote mice,10 TLR4+/+ in non-medullary cells/TLR4-/-in medullary cells (WT/KO) mice,and 10 TLR4-/-in non-medullary cells/TLR4+/+ in medullary cells (KO/WT) heterozygote mice,aged 6-8 weeks,weighing 20-25 g,were used in the study.Lung I/R was induced by occlusion of the left hilum for 60 min followed by 240 min of reperfusion in anesthetized mice.Blood samples were obtained from the femoral artery at 240 min of reperfusion for blood gas analysis,and the oxygenation index (PaO2/FiO2) was calculated.The animals were then sacrificed and lung tissues were immediately removed for determination of wet/dry weight ratio,myeloperoxidase activity and contents of tumor necrosis factor-alpha,interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay) and for microscopic examination of the pathological changes of lungs which were scored.Results Compared with WT/WT mice,the oxygenation index was significantly increased in sequence,and lung injury scores,wet/dry weight ratio,myeloperoxidase activity and contents of tumor necrosis factor-alpha,IL-1β and IL-6 were decreased in sequence in WT/KO,KO/WT and KO/KO mice (P＜0.05).Conclusion TLR4 in non-medullary cells plays a rnore important role in lung I/R injury than that in medullary cells of mice.