HMGB1/TLR4信号通路在大鼠呼吸机相关性肺炎中的作用

Role of HMGB1/TLR4 signaling pathway in ventilator-associated pneumonia in rats

目的探讨高迁移率族蛋白B1(HMGB1)/Toll样受体4(TLR4)信号通路在大鼠呼吸机相关性肺炎(VAP)中的作用。方法将72只大鼠随机分为自主呼吸空白对照组(C组)、正常潮气量机械通气组(V组)、高潮气量机械通气组(HV组),每组各24只。C组大鼠不进行机械通气;V组大鼠进行正常潮气量机械通气,HV组大鼠进行高潮气量机械通气。检测支气管肺泡灌洗液(BALF)中的总蛋白、炎症因子[白细胞介素-6(IL-6)、(IL-10)、肿瘤坏死因子-α(TNF-α)、巨噬细胞炎症因子-2(MIP-2)]、髓过氧化物酶(MPO)、肺组织湿/干重(W/D)比值、肺组织HMGB1和TLR4的mRNA表达量和蛋白表达量。结果V组和HV组大鼠肺组织W/D比值及病理学评分均高于C组(P<0.05),BALF总蛋白、IL-6、IL-10、TNF-α、MIP-2以及MPO水平均高于C组(P<0.05),肺组织HMGB1和TLR4的mRNA表达量、蛋白表达量均高于C组(P<0.05)。结论HMGB1和TLR4与各种炎症介质紧密联系,VAP的机制可能与HMGB1/TLR4信号通路有关。

OBJECTIVE To explore the role of high mobility group protein B1(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway in ventilator-associated pneumonia(VAP)in rats.METHODS Totally 72 rats were randomly divided into the autonomous respiration blank control group(the group C),the normal tidal volume mechanical ventilation group(the group V)and the high tidal volume mechanical ventilation group(the HV group),with 24 rats in each group.The group C was not treated with mechanical ventilation,the group V was given normal tidal volume mechanical ventilation,and the HV group was treated with high tidal volume mechanical ventilation.The total protein,inflammatory factors[interleukin-6(IL-6),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),macrophage inflammatory protein-2(MIP-2)]and myeloperoxidase(MPO)in bronchoalveolar lavage fluid(BALF)as well as wet/dry weight(W/D)of lung tissues,expression quantities of HMGB1 and TLR4 mRNA and protein in lung tissues were detected.RESULTS The W/D and pathological scores of lung tissues of the group V and the group HV were significantly higher than those of the group C(P<0.05);the levels of BALF total protein,IL-6,IL-10,TNF-α,MIP-2 and MPO of the group V and the group HV were significantly higher than those of the group C(P<0.05);the expression quantities of HMGB1 and TLR4 mRNA and protein in lung tissues were significantly higher in the group V and the group HV than in the group C(P<0.05).CONCLUSION HMGB1 and TLR4 are closely related to various types of inflammatory mediators.The mechanism of VAP may be related to the HMGB1/TLR4 signaling pathway.