Lv Tangfeng, Shen Xiaokun, Shi Yi, Song Yong
Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, People's Republic of China.
J Trauma. 2009 Jan;66(1):124-31. doi: 10.1097/TA.0b013e318181e555.
Acute lung injury (ALI) and acute respiratory distress syndrome in patients with hemorrhagic shock (HS) or resuscitation is associated with the expression of TLR4. However, the role of TLR4 in ALI induced by unresuscitated HS remains obscure.
The lung pathologic change was observed by hematoxylin and eosin staining. Interleukin-1beta and tumor necrosis factor-alpha were analyzed by enzyme-linked immunosorbent assay. Polymorphonuclear leukocyte sequestration and lung leak were analyzed by pulmonary myeloperoxidase activity and Evans blue dye. The expressions of TLR4 mRNA and protein were analyzed by reverse transcription-polymerase chain reaction and Western blot, respectively. TLR4 distribution was analyzed by immunohistochemistry.
Lung neutrophil accumulation and microvascular permeability were significantly increased after unresuscitated HS, meanwhile, lung interleukin-1beta and tumor necrosis factor-alpha were gradually augmented. TLR4 mRNA, TLR4 distribution and TLR4 protein were also significantly increased in TLR4 wt mice, however, no above-mentioned changes appeared in TLR4 mutant mice.
TLR4 is strongly associated with the pathogenesis of ALI induced by unresuscitated HS, which may serve as a useful therapeutic target.
失血性休克（HS）或复苏患者的急性肺损伤（ALI）及急性呼吸窘迫综合征与Toll样受体4（TLR4）的表达相关。然而，TLR4在未复苏的HS所致ALI中的作用仍不清楚。
采用苏木精-伊红染色观察肺组织病理变化。通过酶联免疫吸附测定法分析白细胞介素-1β和肿瘤坏死因子-α。通过肺髓过氧化物酶活性和伊文思蓝染料分析多形核白细胞滞留和肺渗漏。分别采用逆转录-聚合酶链反应和蛋白质印迹法分析TLR4 mRNA和蛋白的表达。通过免疫组织化学分析TLR4的分布。
未复苏的HS后肺中性粒细胞积聚和微血管通透性显著增加，同时，肺白细胞介素-1β和肿瘤坏死因子-α逐渐增加。TLR4野生型小鼠的TLR4 mRNA、TLR4分布和TLR4蛋白也显著增加，然而，TLR4突变型小鼠未出现上述变化。
TLR4与未复苏的HS所致ALI的发病机制密切相关，可能是一个有用的治疗靶点。
