【摘要】 目的探讨高迁移率族蛋白B1(HMGB1)/Toll样受体(TLRs)信号通路在大鼠机械通气肺损伤(VILI)中的作用机制。方法 32只健康SD大鼠随机分为4组:正常对照组(N组)不行机械通气,保留自主呼吸;高氧流量组(HN组)氧流量7 L/min;小潮气量机械通气组(LV组)潮气量7 ml/kg;大潮气量机械通气组(HV组)潮气量30 ml/kg。通气4 h后处死动物取肺组织,HE染色观察各组肺组织损伤情况,检测支气管肺泡灌洗液(BALF)中白细胞(WBC)计数、肺湿重干重比值(W/D);ELISA法检测BALF中IL-6、TNF-α、HMGB1水平;Western blot法检测肺组织HMGB1、TLR2、TLR4蛋白的表达。应用单因素方差分析及两样本均数t检验进行不同组间的比较。结果与N组相比,HV组及HN组大鼠肺W/D,BALF中WBC计数,BALF中HMGB1、TNF-α、IL-6水平以及HMGB1、TLR2、TLR4蛋白表达均显著增加,差异有统计学意义(P<0.05);LV组上述各指标与N组相比差异无统计学意义。结论大潮气量机械通气及高氧流量通气均可引起大鼠肺组织急性炎症反应,其机制可能与HMGB1/TLRs信号通路激活有关。更多还原

【Abstract】 Objective The aim of this experiment was to investigate the role of high-mobility group box protein 1(HMGB1) /Toll-like receptors( TLRs) signaling pathway in mechanical ventilation lung injury. Methods 32 healthy male SD rats were randomly divided into the following 4 groups according to tidal volume and the concentration of inhaled oxygen:room air inhalation without mechanical ventilation( N);high concentration of oxygen inhalation(50%) without mechanical ventilation( HN); low tidal volume ventilation with room air inhalation( LV)(7ml / kg); high tidal volume ventilation with room air inhalation( HV)(30 ml / kg). The ventilation lasted for four hours. Then WBC in BALF and the lung W / D were detected. The adapted ELISA was used to determine the concentrations of HMGB1,tumor necrosis factor-α( TNF-α) and interleukin-6( IL-6) in BALF from rat. The histological changes of lung tissue were observed by HE staining. The expressions of HMGB1,TLR4 and TLR2 in lung tissue of all rats were detected by western blot. Results HMGB1,TLR2 and TLR4 expressions,the concentrations of HMGB1,TNF-α and IL-6 in BALF,the WBC in BALF and the lung W / D were significantly higher in HV group and HN group( P < 0. 05). While they were no significant differences in LV group. Conclusion These findings demonstrated that high tidal volume ventilation and high concentration of oxygen inhalation could aggravate lung injury in rats through HMGB1 / TLRs signaling pathway.更多还原