铜绿假单胞菌对TLR4缺失鼠的致病性研究

本研究旨在了解TLR4信号转导在铜绿假单胞菌感染所致急性肺损伤的发病机理中的作用.通过使用Tlr4基因突变致正常TLR4信号转导缺失的C3H/HeJ小鼠,评估TLR4信号转导在调节铜绿假单胞菌引起的急性肺损伤中的作用.选用6～8周龄、雄性、TLR4缺陷型(C3H/HeJ)和SPF级野生型(C3H/HeN)的小鼠各21只...

Pathogenicity of Pseudomonas aeruginosa to TLR4-deficient Mice

This study aims to understand the role of TLR4 signal transduction in the pathogenesis of acute lung injury caused by Pseudomonas aeruginosa infection. C3H/HeJ mice lacking of normal TLR4 signaling due to mutations in Tlr4 gene was used to evaluated the role of TLR4 signaling in the regulation of acute lung injury caused by Pseudomonas aeruginosa. A total of twenty-one TLR4-deficient (C3H/HeJ) male mice and twenty-one SPF wild-type (C3H/HeN) male mice, aged 6-8 weeks, were randomly divided into 4 groups:C3H/HeN control group, C3H/HeJ control group, C3H/HeN infection group, and C3H/HeJ infection group. Mice in the two infection groups were nasally infected with a lethal dose of Pseudomonas aeruginosa. After infection, the survival rate, clinical symptoms, pulmonary pathological changes, lung bacterial load, and the level of cytokines in lungs were observed. The results showed that:1) Compared with the wild-type C3H/HeN infection group, the clinical symptoms of mice in the TLR4-deficient C3H/HeJ infection group were significantly aggravated. The median survival time of mice in the TLR4-deficient C3H/HeJ infection group was shorter. The body temperature of mice in the C3H/HeJ infection group was extremely significantly lower than that in the C3H/HeN infection group after 8 h of infection (P<0.01), and the pulmonary pathological changes and the degree of pulmonary edema were more serious than that of the C3H/HeN infection group (P<0.05); 2) The level of TNF-α and IL-1β in lung of mice in the TLR4-deficient C3H/HeJ infection group extremely significantly lower than that in the wild-type C3H/HeN infection group after 8 h of infection (P<0.01); 3) Mice pulmonary bacterial load in TLR4-deficient C3H/HeJ infection group was significantly higher than that in the wild-type C3H/HeN infection group (P<0.05). In summary, the lack of TLR4 protein significantly increased the pathogenicity of Pseudomonas aeruginosa to mice.