重症社区获得性肺炎患者外周血单核细胞Toll样受体4的表达及临床意义

Expression of Toll-like receptor 4 in mononuclear cells of patients with severe community-acquired pneumonia and its clinical significance

目的探讨重症社区获得性肺炎(SCAP)患者外周血单核细胞Toll样受体4(TLR4)的表达情况及临床意义。方法选择入住呼吸科及ICU的SCAP患者50例为SCAP组,另择同期健康体检者50例作为对照(对照组)。分离两组外周静脉血单核细胞,提取单核细胞的mRNA,采用实时定量PCR检测TLR4 mRNA表达量。采用ELISA法检测两组血清TNF-α和IL等相关炎症因子水平。在两组外周静脉血中加入脂多糖(LPS)后,再次测定TLR4 mRNA表达量及相关炎症因子水平。分析SCAP患者TLR4 mRNA表达量与肺炎严重程度(PSI)评分的相关性。结果 SCAP组外周血单核细胞TLR4 mRNA相对表达量及血清TNF-α、IL-6、IL-8、C反应蛋白(CRP)、降钙素原(PCT)水平均明显高于对照组(均P<0.05);加入LPS后,两组TLR4 mRNA的表达量及血清TNF-α、IL-6、IL-8、CRP水平均较加入LPS前升高(均P<0.05),但SCAP组升高的幅度小于对照组。SCAP组TLR4 mRNA表达量与PSI评分呈正相关(r=0.641,P<0.05)。结论 TLR4信号通路在SCAP发展中起重要作用,外周静脉血单核细胞TLR4受体过表达诱导NF-κB活化及其下游炎症因子释放,是SCAP造成机体损伤的主要病理机制。阻断TLR4受体可以抑制炎症因子的释放,减轻肺组织病理损害,可以为临床治疗SCAP提供新的靶点。

Objective To investigate the expression of toll like receptors 4(TLR4) in peripheral blood mononuclear cells of patients with severe community-acquired pneumonia(SCAP), and explore its clinical significance. Methods Fifty patients with severe community-acquired pneumonia(SCAP group) admitted in Department of Respiration and intensive care unit from 2014 January to 2015 January and 50 healthy subjects were enrolled in the study(control group). Peripheral blood mononuclear cells(PBMCs) were separated and mRNA was extracted, the expression of TLR4 mRNA was detected with real-time quantitative PCR(q RT-PCR) in both groups. Enzyme-linked immunosorbent assay(ELISA) was used to detect tumor necrosis factor(TNF-α), IL-6,IL-8 and other related inflammatory factors in serum of two groups. After lipopolysaccharide(LPS) was added into peripheral venous blood, TLR4 mRNA and related inflammatory factors was detected. The correlation between TLR4 mRNA expression and pneumonia severity index(PSI) score in SCAP patients was analyzed. Results The relative expression of TLR4 mRNA and the levels of inflammatory cytokines in SCAP group were significantly higher than those in control group(P<0.05). After adding LPS,the levels of TLR4 mRNA expression and inflammatory factors were increased in both groups, but the levels were increased less markedly in SCAP group. The expression of TLR4 mRNA was positively correlated with the score of PSI in SCAP group.Conclusion The TLR4 signal pathway is involved in the development of SCAP. Blocking TLR4 receptor may inhibit the release of inflammatory cytokines and reduce lung tissue damage, which may provide a new target for clinical treatment of SCAP.