内毒素急性肺损伤TLR4-LPS信号传导对NF-κB活性的影响

Influence of LPS-TLR4 signal transduction pathway on NF-κB in endotoxin-induced acute lung injury

目的本文旨通过检测肺组织TLR4、NF-κB表达及支气管肺泡灌洗液炎症因子含量,探讨TLR4/NF-Kb信号在ALI发病中的作用。方法 30只大鼠随机分为对照组、ALI组和干预组。静脉注射LPS构建肺损伤模型,实时定量PCR及western blot检测肺组织TLR4、NF-κB表达,ELISA法检测TNF-α、IL-1β浓度。结果肺损伤评分:ALI组>TLR4拮抗剂干预组>对照组,肺泡灌洗液TNF-α、IL-1β浓度较对照组分别增加了7倍和3.5倍。ALI组肺组织中TLR4和NF-κB表达明显增加,TLR4拮抗剂能抑制二者表达。结论 TLR4/NF-κB信号通路在脂多糖大鼠急性肺损伤模型的发展过程中起重要作用,TLR-4受体过表达诱导NF-κB活化及其下游炎症因子释放,加重急性肺损伤。

Objective To investigate the expression of Toll-like receptor 4 and nuclear factor-KB in lung tissue and bronchoalveolar lavage fluid and to determine the role of TLR4/NF-κB signaling pathway on the pathogenesis of ALl. Methods 30 rats were randomly divided into three groups. The model of ALI was created by injecting LPS, and the levels of TNF-a and IL-1β were determined in bronchoalveolar lavage fluid by ELISA. Real-time PCR was used to detect TLR4 and NF-KB mRNA levels. TLR4 and NF-KB protein expression was determined by Western blot. Results The score of ALl was higher in the ALI group than in the TLR4 blocking and control group. The injection of LPS resulted in a significant increase in TNF-a and IL-1β. The expression of TLR4 and NF-κB increased more obvi- ously in the ALI group than in the control group. Conclusion TLR4/NF-κB signal transduction pathway may play an important role in acute lung injury. The high expression of TLR4 may induce the expression of NF-KB and its downstream genes, which can worsen the damage of lung.