Mechanisms of protein kinase C and tyrosine kinase in mechanical ventilation-induced lung injury
Zhao Tao
Zheng Shengfa
Li Gang
Han Yongbin
Lyu Gang
Abstract：Objective To investigate the mechanisms of protein kinase C (PKC) and tyrosine kinase (c-Src) in mechanical ventilation-induced lung injury(VILI).Methods Thirty healthy specific pathogen free C57BL/6J mice were randomly divided into 5 groups:normal low tidal volume group(group C),high tidal volume group(group H),high tidal volume + c-Src inhibitor group(group H + P),high tidal volume + PKCα inhibitor group(group H + B),high tidal volume + c-Src inhibitor + PKCα inhibitor group(group H + P + B),with 6 mice in each group.Group C was treated by low tidal volume mechanical ventilation:tidal volume =7 ml/kg,respiratory rate =120 times/min,end-expiratory positive pressure =5 cmH2O;group H,group H + P,group H + B and group H + P + B were treated by high tidal volume mechanical ventilation:tidal volume =20 ml/kg,respiratory rate =40 times/min,end-expiratory positive pressure =0 cmH2O;inspiratory-to-expiratory ratio was 1 ∶ 2;duration of ventilation was 4 h.Group H + P and group H + P + B had intramuscular injection of c-Src inhibitor PP2 (1 μg/kg) 1 h before anesthesia;group H + B and group H + P + B had intramuscular injection of PKCα inhibitor BIM(0.12 mg/kg) 1 h before anesthesia.The mice were executed after mechanical ventilation and lung tissues were separated.Pathological score of lung injury was assessed.Wet-to-dry weight ratio of lung tissue was measured.Expressions of p120-catenin,PKCα and c-Src were tested by Western blot.Results Pathological score of lung injury and wet-to-dry weight ratio of lung tissue in group H were significantly higher than those in group C,group H + P,group H + B and group H + P + B (P ＜ 0.05).Expression of p120-catenin in group H was significantly lower than that in group C,expressions of PKCα and p-c-Src in group H were significantly higher than those in group C [(0.361± 0.040) vs (0.818±0.025),(0.731 ±0.046) vs (0.324±0.032),(0.655 ±0.040) vs (0.207 ±0.045)] (P ＜ O.05).Expression of p120-catenin in group H + P,group H + B and group H + P + B [(0.714 ± 0.030),(0.734 ± 0.027),(0.816 ± 0.020)] were significantly higher than that in group H (P ＜ 0.05).Expression of p-c-Src in group H + B was significantly lower than that in group H [(0.268 ± 0.053)(0.655 ± 0.040)] (P ＜ 0.05).Conclusions PKCα and c-Src are involved in VILI.High tidal volume mechanical ventilation activates PKCα mediating the phosphorylation of c-Src to decrease the expression of p120-catenin.
Keywords：Mechanical ventilation-induced lung injuryp120-cateninProtein kinase CTyrosine kinase
Publication Date：2018-01-01
Online Publishing Date：2026-09-14(First online date of this platform, not the publication date of the document)
Pages：4( 537-540 )