Th17细胞相关因子在重症肺炎克雷伯菌肺炎大鼠中的调控作用

Role of Th-17 related cytokines in rats with severe pneumonia induced by Klebsiella pneumoniae

目的探究辅助性T细胞17(Th-17)相关因子在重症肺炎克雷伯菌肺炎发病过程中的调控作用。方法将60只SD大鼠随机分为对照组(10只)和重症肺炎组(50只),采用气管滴注肺炎克雷伯菌建立重症肺炎大鼠模型,重症肺炎组根据肺炎克雷伯菌感染时间分为12 h组、1 d组、3 d组、5 d组和7 d组,每组各10只。观察大鼠行为学变化、肺组织形态学变化,检测肺泡灌洗液中白细胞和中性粒细胞的数量,采用ELISA检测肺泡灌洗液中白细胞介素17(IL-17)、白细胞介素23(IL-23)、肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)的表达。分析中性粒细胞数目与IL-17、IL-23水平的相关性。结果与对照组相比,重症肺炎组大鼠出现明显的感染症状,呼吸加重、颜面部和四肢呈紫绛色等,且肺组织表现出明显病变,接种第3天最为严重;肺泡灌洗液中白细胞和中性粒细胞的数目、IL-17、IL-23、TNF-α、IL-1β水平显著升高(P<0.05),白细胞和中性粒细胞的数目、IL-17、IL-23水平于第3天达到峰值,TNF-α、IL-1β水平于第5天达到峰值;肺泡灌洗液中IL-17、IL-23水平分别与中性粒细胞的数目呈正相关(P<0.05)。结论IL-17、IL-23为重症肺炎克雷伯菌肺炎中早期促炎因子,可通过刺激中性粒细胞的活性,参与重症肺炎的发生发展。

Objective To explore the regulatory role of T helper cell 17 related cytokines in the pathogenesis of severe Klebsiella pneumonia.Methods 60 SD rats were randomly divided into control group(n=10)and severe pneumonia group(n=50).The model of severe pneumonia rats was established by intratracheally instilled with Klebsiella pneumoniae.According to time of Klebsiella pneumonia infection,the severe pneumonia groups were divided into 12h group,1d group,3d group,5d group and 7d group,with 10 cases in each group.The behavioral changes of rats and morphological changes of rats'lung tissues were observed.The number of leucocytes and neutrophils in alveolar lavage fluid was counted.ELISA was performed to detect the expression of IL-17,IL-23,TNF-αand IL-1βin alveolar lavage fluid.The correlation between the number of neutrophils and the levels of IL-17 and IL-23 was analyzed.Results Compared with the control group,there were obvious infection symptoms in severe pneumonia group,including heavier breathing and purple color in face and limbs;there were obvious lesions in lung tissues,with the third day of infection the most serious;the number of leukocytes and neutrophils and the levels of IL-17,IL-23,TNF-αand IL-1βin alveolar lavage fluid were significantly increased(P<0.05).The number of leukocytes and neutrophils and the levels of IL-17 and IL-23 peaked on the third day,while the levels of TNF-αand IL-1βpeaked on the 5th day.The levels of IL-17 and IL-23 in alveolar lavage fluid were positively correlated with number of neutrophils(P<0.05).Conclusion IL-17 and IL-23 are early pro-inflammatory factors of severe Klebsiella pneumonia.They participate in the development of severe pneumonia by stimulating the activity of neutrophils.