NLRP3炎性小体在呼吸机相关性肺炎患者中的表达及临床意义

目的观察核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptors family pyrin domain containing 3,NLRP3)炎性小体在呼吸机相关性肺炎(ventilator-associated pneumonia,VAP)患者中的表达及临床意义。方法选取2014年1月至2019年1月于本院行机械辅助通气治疗的患者720例作为研究对象。根据是否发生VAP,将其分为VAP组(132例)和非VAP组(588例),按VAP患者病情严重程度将VAP组分为低危组(48例)、中危组(44例)和高危组(40例)。检测各组单个核细胞(peripheral blood mononuclear cells,PBMCs)中NLRP3、半胱氨酸蛋白酶1(Caspase-1)mRNA表达及白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor,TNF-α)水平,评价NLRP3水平对VAP患者病情严重程度的预测价值。结果VAP组患者外周血NLRP3、Caspase-1 mRNA水平及外周血IL-1β和TNF-α水平显著高于非VAP组(P<0.05);VAP患者中高危组外周血NLRP3、Caspase-1 mRNA水平、急性生理学与慢性健康状况评分(acute physiology and chronic health evaluation score,APACHE II score)及外周血IL-1β和TNF-α水平最高,中危组次之,低危组最低。VAP组患者PBMCs NLRP3 mRNA表达与Caspase-1 mRNA、APACHE II评分、外周血IL-1β和TNF-α水平呈显著正相关(Caspase-1 mRNA:r=0.790,P<0.001;APACHE II评分:r=0.752,P<0.001;IL-1β:r=0.710,P=0.003;TNF-α:r=0.740,P<0.001)。ROC曲线分析显示,NLRP3 mRNA水平曲线下面积为0.862(95%CI 0.799~0.925),其最佳工作点为2.16,此时预测VAP患者病情严重程度的灵敏度和特异性分别为75.21%和81.69%,显著优于APACHE II评分、IL-1β及TNF-α。结论外周血NLRP3炎性小体与VAP的发生、发展密切相关,对于VAP患者病情严重程度的预测,具有一定的临床应用价值。

The Expression Level and Clinical Significance of NLRP3 Inflammasome in Patients with Ventilator-associated Pneumonia

Objective To observe the expression level and investigate the clinical significance of nucleotide-binding oligomerization domain-like receptors family pyrin domain containing 3(NLRP3)inflammasome in patients with ventilator-associated pneumonia(VAP).Methods A total of 720 patients who underwent mechanical assisted ventilation were enrolled for the study from January,2014 to February,2019 in our hospital.According to whether VAP occurred,these patients were divided into the VAP group(132 cases)and non-VAP group(588 cases).According to the severity of VAP patients,they were further divided into the low risk group(48 cases),moderate risk group(44 cases)and high risk group(40 cases).At the same time,50 healthy subjects were selected as the control group.The levels of NLRP3 and Caspase-1 mRNA in mononuclear cells,as well as interleukin-1β(IL-1β)and tumor necrosis factor(TNF-α)were detected in all the groups.The predictive value of NLRP3 was evaluated for the severity of VAP patients.Results The levels of NLRP3 and Caspase-1 mRNA,IL-1βand TNF-αin peripheral blood in patients with VAP were significantly higher than in the non-VAP group(P<0.05).The levels of NLRP3 and Caspase-1 mRNA,acute physiology and chronic health evaluation score(APACHE II score),IL-1βand TNF-αin peripheral blood in the high-risk group were the highest,while the middle-risk group was the second,and the low-risk group was the lowest.The level of NLRP3 mRNA in peripheral blood in patients with VAP was positively correlation with Caspase-1 mRNA,APACHE II score,IL-1βand TNF-α(Caspase-1 mRNA:r=0.790,P<0.001;APACHE II score:r=0.752,P<0.001;IL-1β:r=0.710,P=0.003;TNF-α:r=0.740,P<0.001).ROC curve analysis showed that the area under the curve of NLRP3 mRNA was 0.862(95%CI 0.799-0.925),and optimal operating point(OOP)was 2.16,with 75.21%of sensitivity and 81.69%of specificity in predicting the severity of VAP,which were significantly better than APACHE II score,IL-1βand TNF-α.Conclusion The levels of NLRP3 inflammasome in peripheral blood is closely related to the occurrence and development of VAP,which has certain clinical application value for predicting the severity of VAP.