摘要
目的探讨呼吸机相关性肺炎(VAP)患者病原菌分布及白细胞介素35(IL-35)的炎症控制机制。方法回顾性分析2016年12月至2018年12月在我院重症监护病房(ICU)行机械通气的152例患者的临床资料,根据是否发生VAP将其分为VAP组(n=70)和对照组(n=82)。收集VAP患者痰液进行细菌培养及药敏实验,检测并比较两组患者外周血单个核细胞(PBMCs)中CD4^+CD25^+CD127dim/-调节性T细胞(Tregs)比例及血清中白细胞介素35(IL-35)、肿瘤坏死因子α(TNF-α)、干扰素-γ(IFN-γ)水平;同时检测并比较经佛波酯和重组人IL-35刺激后的Tregs细胞培养液上清中IL-35、IFN-γ、TNF-α水平。结果70例VAP患者共检出病原菌128株,其中革兰阴性菌占82.81%,革兰阳性菌占14.84%,真菌占2.34%。鲍曼不动杆菌对头孢西丁的耐药率最高,对头孢哌酮的耐药率最低。铜绿假单胞菌对头孢西丁的耐药率最高,对亚胺培南的耐药率最低。肺炎克雷伯菌对头孢西丁的耐药率最高,对头孢哌酮的耐药率最低。VAP组患者PBMCs中CD4^+CD25^+CD127dim/-Tregs比例及血清中IL-35、IFN-γ、TNF-α水平显著高于对照组(t=12.675、36.631、13.464、8.482,均P<0.001)。经重组人IL-35刺激后的Tregs细胞培养液上清中IL-35水平显著高于佛波酯刺激后(t=8.886,P<0.001)。经重组人IL-35刺激后的Tregs细胞培养液上清中IFN-γ、TNF-α水平显著低于佛波酯刺激后(t=14.091、7.588、均P<0.001)。结论呼吸机相关性肺炎病原菌以革兰阴性菌为主,呈现多药耐药性,临床应合理使用抗菌药物以防治呼吸机相关性肺炎。IL-35可通过调控Tregs功能降低促炎因子分泌从而在呼吸机相关性肺炎发病过程中发挥抗炎症作用,提示IL-35可能为呼吸机相关性肺炎的治疗提供新的方向。
Objective To investigate the pathogen distribution and inflammation control mechanism of interleukin-35(IL-35)in ventilator-associated pneumonia(VAP).Methods The clinical data of 152 patients with mechanical ventilation in the intensive care unit(ICU)of our hospital from December 2016 to December 2018 were retrospectively analyzed.The patients were divided into two groups according to the presence or absence of VAP,namely,VAP group(n=70)and control group(n=82).The sputum of VAP patients was collected for bacterial culturing and drug sensitivity test.The ratio of CD4^+CD25^+CD127 dim/-regulatory T cells(Tregs)in peripheral blood mononuclear cells(PBMCs)and serum levels of interleukin-35(IL-35),tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)were detected and compared between the two groups.Then the levels of IL-35,IFN-γand TNF-αin the culture supernatant of Tregs cells stimulated by phorbol ester and recombinant human IL-35 were detected and compared between groups.Results A total of 128 strains of pathogenic bacteria were isolated from 70 VAP patients,among which 82.81%were Gram-negative bacteria,14.84%were Gram-positive bacteria,and 2.34%were fungi.Acinetobacter baumannii had the highest resistance to Cefoxitin and the lowest resistance to Cefoperazone.Pseudomonas aeruginosa had the highest resistance to Cefoxitin and the lowest resistance to Imipenem.Klebsiella pneumoniae had the highest resistance to Cefoxitin and the lowest resistance to Cefoperazone.The ratio of CD4^+CD25^+CD127 dim/-Tregs and serum levels of IL-35,IFN-γand TNF-αin PBMCs of VAP group were significantly higher than those of control group(t=12.675,36.631,13.464,8.482;all P<0.001).The level of IL-35 in the culture supernatant of Tregs cells stimulated by recombinant human IL-35 was significantly higher than that after phorbol ester stimulation(t=8.886,P<0.001).The levels of IFN-γand TNF-αin the supernatant of Tregs cells stimulated by recombinant human IL-35 were significantly lower than those after phorbol ester stimulation(t=14.091,7.588;all P<0.001).Conclusion The pathogens of VAP are mainly Gram-negative bacteria showing multi-drug resistance,so antibiotics should be used rationally to prevent VAP infection.IL-35 can reduce the secretion of pro-inflammatory factors by regulating Tregs function.Therefore,it plays an anti-inflammatory role in the pathogenesis of VAP,suggesting that IL-35 may provide a new direction for the treatment of VAP.
作者
周蓉
曾令军
潘英
曾小英
奉婷
ZHOU Rong;ZENG Lingjun;PAN Ying;ZENG Xiaoying;FENG Ting(Department of Respiratory Medicine,the First People′s Hospital of Ziyang,Ziyang,Sichuan 641300,China;不详)
出处
《中国微生态学杂志》
CAS
CSCD
2020年第10期1194-1198,共5页
Chinese Journal of Microecology
关键词
呼吸机相关性肺炎
病原菌
耐药性
IL-35
调节性T细胞
促炎因子
Ventilator-associated pneumonia
Pathogenic bacteria
Drug resistance
IL-35
Regulatory T cells
Proinflammatory factor
