论文部分内容阅读
目的观察Toll样受体4(toll-like receptor 4,TLR4)基因突变型小鼠与野生型小鼠内毒素攻击致急性肺损伤(acute lung injury,ALI)的差异,分析TLR4在ALI中的作用。方法采用TLR4基因突变小鼠(C3H/HeJ品系,TLR4~(-/-)及野生型小鼠(CBA品系,TLR4~(+/+)),用内毒素攻击复制小鼠ALI模型,用显微病理及肺干湿重比(W/D)分析肺损伤程度,检测肺组织髓过氧化物酶(MPO)水平,探讨损伤差异的可能机制。结果用1,5 mg·kg~(-1)LPS溶液经尾静脉注射复制ALI模型,结果示TLR4突变小鼠肺组织大体及显微病理损伤较野生型小鼠减轻,同时肺组织水肿(W/D)亦较野生小鼠减轻,尤其是在大剂量(5mg·kg~(-1))时,差异有显著性[(4．08±0．1)vs．(4．55±0．2),n=10,t=12．71,P＜0．01]。突变小鼠肺组织PMN浸润水平较野生型低[MPO：1 mg·kg~(-1)组,(20．73±4．58)vs．(39．97±3．66),n=10,t=13．43,P＜0．01]；5 mg·kg~(-1)组,[(24．0±3．94)vs．(48．5±4．07),n=10,t=15．33,P＜0．01],且两者均较假手术组高。结论TLR4可能通过介导中性粒细胞肺内聚集而导致ALI的发生发展。
Objective To investigate the difference of TLR4 in acute lung injury (ALI) induced by endotoxemia in mice with toll-like receptor 4 (TLR4) gene mutation and wild-type mice and analyze the role of TLR4 in ALI . Methods The TLR4 gene mutant mice (C3H / HeJ strain, TLR4 ~ (- / -) and wild type mice (CBA strain, TLR4 ~ (+ / +)) were used to replicate mouse ALI model with endotoxin challenge Pathology and lung wet / dry weight ratio (W / D) were used to analyze the degree of lung injury and to detect the level of myeloperoxidase (MPO) in lung tissue and to explore the possible mechanism of the difference in the injury.Results With 1 mg / kg ) LPS solution was injected into the tail vein to duplicate the ALI model. The results showed that the general and microscopic pathological lesions of the lung tissue of the TLR4 mutant mice were alleviated compared with the wild type mice, and the lung tissue edema (W / D) At high dose (5 mg · kg -1), the difference was significant [(4.08 ± 0.1) vs. (4.55 ± 0.2), n = 10, t = 12.71 , P <0.01] .The PMN infiltration in the lung tissue of the mutant mice was lower than that of the wild type [MPO: 1 mg · kg -1, (20.73 ± 4.58) vs. (39.97 ± 3.66), n = 10, t = 13.43, P <0.01]. In the group of 5 mg · kg -1, [(24.0 ± 3.94) vs. (48.5 ± 4.07), n = 10, t = 15.33, P <0.01], and both were higher than those in sham operation group.Conclusion TLR4 may induce the occurrence of ALI by mediating the intrapulmonary neutrophil aggregation development of.