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.%目的：探讨 Toll 样受体4（TLR4）及其相关信号链酶在不同潮气量机械通气大鼠肺组织中的表达变化。方法按随机数字表法将40只 SD 大鼠分为5组，每组8只。A 组仅切开气管保留自主呼吸，B1组和 B2组以潮气量6 mL/ kg 分别通气1 h 和2 h，C1组和 C2组以潮气量30 mL/ kg 分别通气1 h 和2 h。A 组在气管切开即刻，其余各组在机械通气结束时处死大鼠。光镜下观察各组大鼠肺组织病理改变，免疫组化法检测肺组织中TLR4、肿瘤坏死因子受体相关因子6（TRAF6）、白细胞介素1受体相关激酶4（IRAK4）及核转录因子-κB（NF -κB）p65蛋白的表达，RT - PCR 检测 TLR4 mRNA 的表达，测定肺组织髓过氧化物酶（MPO）的活性，计算肺湿干重比值（W/ D 比值），ELISA 法测定支气管肺泡灌洗液中肿瘤坏死因子-α（TNF -α）的浓度。结果 A 组、B1组、B2组之间肺组织 TLR4 mRNA 表达，TLR4、TRAF6、IRAK4、NF -κBp65蛋白的表达，W/ D 比值，MPO 活性和 TNF -α浓度差异均无统计学意义（P >0.05）。与相应 B1、B2组比较，C1、C2组 TLR4 mRNA 和 TLR4、TRAF6、IRAK4、NF -κBp65蛋白表达明显上调，W/ D 比值、MPO 活性和 TNF -α浓度明显升高，差异均有统计学意义（P <0.05）。随通气时间延长，C2组各指标较 C1组改变更为明显（P <0.05）。结论 TLR4及其相关信号链酶在肺组织中的表达参与了机械通气相关性肺损伤的发生与发展。
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