• Ruili Fu, Linghui Pan, Fei Lin, Wanyun Ge, Cuiyuan Huang, and Huijun Dai.
• Department of Anesthesiology, the Affiliated Tumor Hospital, Guangxi Medical University, Nanning 530021, Guangxi, China, Corresponding author: Pan Linghui, Email: plinghui@hotmail.com.
• Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2014 Dec 1;26(12):865-9.

ObjectiveTo evaluate the role of Toll-like receptor 2/nuclear factor-ΚB (TLR2/NF-ΚB) signaling pathway pretreatment in ventilator-induced lung injury (VILI).MethodsThirty male Sprague-Dawley (SD) rats were randomly divided into three groups by using random number scale, with 10 rats in each group. Group A: rats were given 200 μL of TLR2 monoclonal antibodies (TLR2mAb, 10 μg/kg) by slow instillation through tracheal catheter, and then ventilated with a high tidal volume (VT) of 40 mL/kg. Group B: ventilated with a normal VT of 8 mL/kg. Group C: rats were tracheally instilled with 10 μg/kg of TLR2mAb devoid of biologic activity, and then ventilated with a high VT of 40 mL/kg. The rats were mechanically ventilated for 4 hours, the lung wet to dry weight ratio (W/D) was calculated. The changes in pathology and ultrastructure in lung tissue were observed with microscope. Enzyme linked immunosorbent assay (ELISA) was performed to determine the concentration of interleukins (IL-1β, IL-6) and tumor necrosis factor-α (TNF-α) in serum and brconchoalveolar lavage fluid (BALF). Real-time fluorescent quantitation reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the mRNA expressions of TLR2, NF-ΚB and myeloid differentiation factor 88 (MyD88) in lung tissue.ResultsNo obvious pathological changes in lungs were found in group A and group B, and no obvious damages to ultra-microstructure were found in lung macrophages, typeI epithelial cell and typeII epithelial cell. In group C, pathological changes were observed, including pulmonary alveoli fusion, alveoli septum thickening, inflammatory cells infiltration, and damages to ultrastructure of lung macrophage, damage to cell membrane of typeI epithelial cells and type II epithelial cells, vacuoles in cytoplasm, damage to organelle, and even pyknosis and perinuclear cistern thickening. Compared with group C, W/D ratio and mean concentration of inflammatory cytokines in serum and BALF showed a significant decrease in group A and B [W/D ratio: 1.151 ± 0.026, 1.128 ± 0.048 vs. 1.403 ± 0.062; concentration of IL-1β in serum (ng/L): 37.05 ± 5.61, 34.52 ± 4.31 vs. 51.45 ± 8.18; concentration of IL-6 in serum (ng/L): 53.65 ± 5.16, 55.77 ± 5.62 vs. 89.96 ± 7.08; concentration of TNF-α in serum (ng/L): 71.93 ± 13.29, 67.36 ± 11.42 vs. 96.20 ± 11.60; concentration of IL-1β in BALF (ng/L): 56.48 ± 6.16, 54.44 ± 7.26 vs. 99.77 ± 8.41; concentration of IL-6 in BALF (ng/L): 172.44 ± 21.26, 163.47±18.70 vs. 216.22 ± 23.90; concentration of TNF-α in BALF (ng/L): 235.81 ± 42.75, 231.72 ± 40.38 vs. 374.85 ± 69.61, all P<0.01], but there were no significant differences between group A and group B (all P>0.05). The mRNA expressions of TLR2, MyD88, and NF-ΚB were significantly decreased in group A and group B compared with those in group C [TLR2 mRNA(2(-Δ ΔCt)):1.021 ± 0.287, 0.938 ± 0.196 vs. 3.862 ± 0.871; MyD88 mRNA(2(-Δ ΔCt)):1.235 ± 0.277, 1.300 ± 0.306 vs. 3.618 ± 1.107; NF-ΚB mRNA(2(-Δ ΔCt)):0.519 ± 0.036, 1.043 ± 0.170 vs. 20.280 ± 9.466, P<0.05 or P<0.01], but there was no significant difference among the parameters mentioned above between group A and B (all P>0.05).ConclusionsTo some extent, pre-intervention with TLR2mAb to block the TLR2/NF-ΚB signal pathway can inhibit the release of pro-inflammatory factors, and regulate the VILI.

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