铜绿假单胞菌对TLR4缺失鼠的致病性研究

doi:10.11843/j.issn.0366-6964.2022.03.023

摘要/Abstract

摘要： 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,随机分为4组:C3H/HeN对照组、C3H/HeJ对照组、C3H/HeN感染组和C3H/HeJ感染组。将两个感染组的小鼠滴鼻感染致死剂量的铜绿假单胞菌。评估各组小鼠的存活率、临床症状,肺病变程度、肺细菌载量以及肺部细胞因子含量的动态变化。结果表明:1)与野生型C3H/HeN感染组小鼠相比,TLR4缺陷型C3H/HeJ感染组小鼠临床症状明显加重。其中,TLR4缺陷型C3H/HeJ感染组小鼠中位生存期更短;感染后8 h,C3H/HeJ感染组小鼠体温极显著低于C3H/HeN感染组(P<0.01),肺组织大体病变更严重,肺水肿程度显著高于C3H/HeN感染组(P<0.05);2)感染后8 h,TLR4缺陷型C3H/HeJ感染组小鼠肺匀浆中TNF-α和IL-1β含量极显著低于野生型C3H/HeN感染组小鼠(P<0.01);3) TLR4缺陷型C3H/HeJ感染组小鼠肺细菌载量显著高于野生型C3H/HeN感染组(P<0.05)。综上,TLR4蛋白缺失显著增加了铜绿假单胞菌对小鼠的致病性。

关键词: 铜绿假单胞菌, TLR4缺失鼠, 细菌载量, 细胞因子, 免疫病理, 肺损伤

Abstract: 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.

Key words: Pseudomonas aeruginosa, TLR4-deficient mice, bacterial load, cytokine, immunopathology, lung injury

中图分类号:

S855.1

白江松, 张子卉, 连朋敬, 奚柳青, 李静云, 徐彤, 李鸿儒, 张钟方, 乔健. 铜绿假单胞菌对TLR4缺失鼠的致病性研究[J]. 畜牧兽医学报, 2022, 53(3): 904-912.

BAI Jiangsong, ZHANG Zihui, LIAN Pengjing, XI Liuqing, LI Jingyun, XU Tong, LI Hongru, ZHANG Zhongfang, QIAO Jian. Pathogenicity of Pseudomonas aeruginosa to TLR4-deficient Mice[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(3): 904-912.

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