摘要
Abstract
Objective To investigate the expression of Toll - like receptor 4(TLR4)under different ventilator conditions and to explain the relationship between the expressions of TLR4 and the activation of downstream signals in lung tissue in stress injury model. Methods Forty healthy male SD rats were randomly assigned into 5 groups( n = 8):Group A(spontaneous breathing),Group B1 and B2(VT at 6 mL/ kg,durations of 1 h and 2 h,respectively),and Group C1 and C2(VT at 30 mL/ kg,durations of 1 h or 2 h,respectively). After maintaining ventilation for 1 h or 2 h, all rats were sacrificed and specimens of lung tissues and bronchoalveolar lavage fluid(BALF)were harvested. Lung path-ological changes were observed by microscopy. The protein levels of TLR4,tumor necrosis factor receptor - associated fac-tor 6(TRAF6),interleukin - 1 receptor - associated kinase 4(IRAK4)and nuclear factor - kappaB p65(NF - κBp65) in lung tissues were assayed with immunohistochemistry staining. The expression levels of TLR4 mRNA in lung tissue were measured by RT - PCR. Lung myeloperoxidase(MPO)activity was measured by colorimetric analysis,and wet - dry weight ratio(W/ D ratio)was also measured. The levels of tumor necrosis factor - α(TNF - α)in BALF were measured by ELISA. Results There was no significant difference in the expression of TLR4 mRNA and TLR4,TRAF6,IRAK4 and NF - κBp65 proteins,as well as W/ D ratio,MPO and TNF - α in BALF among Group A,Group B1 and Group B2 (all P > 0. 05). The expression of TLR4 mRNA and TLR4,TRAF6,IRAK4,NF - κBp65 proteins were significantly up- regulated,while W/ D ratio,MPO and TNF - α in BALF were also significantly increased in Group C1 and Group C2 than in Group B1 and Group B2 accordingly(all P < 0. 05). Each index changes were significantly more prominent in Group C2 than Group C1(all P < 0. 05). Conclusion TLR4 and the activation of the downstream signals in lung tissue participate in the development of ventilator - induced lung injury.关键词
Toll 样受体 4/肿瘤坏死因子受体相关因子 6/白细胞介素 1 受体相关激酶 4/核转录因子 - κBKey words
Toll - like receptor 4/tumor necrosis factor receptor - associated factor 6/interleukin - 1 receptor -associated kinase 4/nuclear factor - κB