脂磷壁酸对小鼠子宫内膜组织和内膜细胞中功能受体TLR2表达的影响

Effect of Lipoteichoic Acid on Functional Receptor TLR2 Expression in Endometrial Tissue and Cell of Mice

革兰阳性菌是引起子宫内膜炎的主要原因之一,而脂磷壁酸(lipoteichoic acid,LTA)则是革兰阳性菌细胞壁中的重要组成部分。Toll样受体2(Toll-like receptor 2,TLR2)是天然免疫系统识别病原微生物的主要受体,在天然免疫反应中具有重要的作用,与革兰阳性菌引起的子宫内膜炎密切相关。本研究以小鼠为模型,采用不同浓度的LTA在体子宫内灌注和对体外子宫内膜上皮细胞系采用不同浓度的LTA刺激,观察小鼠子宫内膜组织的病理组织学变化,子宫内膜组织中TLR2表达的变化,以及炎性细胞因子TNF-α、IL-6的表达水平,为TLR2介导的炎性信号通路的研究提供一定的依据。结果表明,从子宫灌注不同浓度LTA后可引起急性子宫内膜炎,子宫内膜组织中炎性细胞增多,LTA刺激后子宫内膜组织中TLR2、TNF-α、IL-6mRNA表达量明显升高,随刺激浓度的变化而变化,低浓度(≤0.1μg.mL-1)增强而高浓度(>0.1μg.mL-1)下降。本试验中在LTA感染后TLR2、TNF-α、IL-6mRNA表达均升高,说明TNF-α、IL-6mRNA表达变化与TLR2相一致,提示TLR2介导转录因子NF-κB的信号途径,使炎性细胞因子TNF-α、IL-6大量表达。

Endometritis is one of the three severe diseases in dairy cows, which has serious impact on the development of dairy industry. Gram-positive bacteria are the major pathogens of endometritis. Lipoteichoic acid （LTA） is important component of the cell wall of Gram-positive bacteria. Toll-like receptor 2 （TLR2） is the main receptor of innate immune system, which recognizes pathogenic microorganisms and plays significant role in innate immune reaction. TLR2 has close relationship with endometritis caused by Gram-positive bacteria. In this study, mice were used as model, and uterus infusion was taken with different concentration of LTA. Meanwhile, endometrial epithelia cell culture was stimulated with different concentration of LTA in vitro. Pathological histological changes of endometrial tissue in mice were observed, and expression level of TLR2 and inflammatory cytokine TNF-α, IL-6 in endometrial tissue of mice was analyzed. The results could provide some basis for inflammatory signal pathway mediated by TLR2. The results indicated that infusion of different concentration of LTA led to acute endometritis, and inflammatory cells increased in endometrial tissues. Expression of TLR2, TNF-α, IL-6 mRNA in endometrial tissues and epithelial cells increased significantly after different concentrations of LTA stimulation. The expression level changed depending on LTA concentration. Low concentration led to high level expression, however, high concentration decreased expression level.