肺结核患者支气管肺泡灌洗液miRNA-431、Notch2表达与结核杆菌耐药性的关系

The correlation between expression of miR-431 and Notch2 in bronchoalveolar lavage fluid and drug resistance of Mycobacterium tuberculosis

目的探讨肺结核患者支气管肺泡灌洗液微小RNA-431(miR-431)、Notch2表达与结核杆菌耐药性的关系。方法选取153例耐药肺结核患者(耐药组)、167例非耐药肺结核患者(非耐药组)、120例肺部检查无异常者(对照组)作为研究对象,根据耐药情况将耐药组分为耐多药组(112例)、广泛耐药组(41例)。采用荧光实时定量聚合酶链反应(qRT-PCR)检测支气管肺泡灌洗液中miR-431、Notch2表达并进行比较;分析耐药组miR-431、Notch2表达与患者临床病理特征关系;采用Spearman分析相关性;采用多因素logistic回归分析影响结核病患者耐药的因素。结果对照组、非耐药组、耐药组支气管肺泡灌洗液中miR-431、Notch2表达差异均有统计学意义(P<0.05)。与对照组相比,非耐药组、耐药组支气管肺泡灌洗液中miR-431表达均较高(P<0.05),Notch2表达均较低(P<0.05);与非耐药组相比,耐药组支气管肺泡灌洗液中miR-431表达均较高(P<0.05),Notch2表达均较低(P<0.05)。与耐多药组相比,广泛耐药组支气管肺泡灌洗液中miR-431表达均较高(P<0.05),Notch2表达均较低(P<0.05)。耐药组miR-431、Notch2表达与性别、结核空洞均无关(P>0.05),与年龄、吸烟史、耐药情况、病灶所占肺野均有关(P<0.05);Spearman分析结果显示,耐药组支气管肺泡灌洗液中miR-431、Notch2表达呈负相关(P<0.05);多因素logistic回归分析结果显示,病灶所占肺野>3个、miR-431高表达均是结核病患者发生耐药性的独立危险因素(P<0.05),Notch2高表达是独立保护因素(P<0.05)。结论miR-431、Notch2可能参与肺结核患者耐药性的形成,可能成为临床生物标志物。

Objective To investigate the correlations between expression of miR-431 and Notch2 in bronchoalveolar lavage fluid and drug resistance of Mycobacterium tuberculosis.Methods There were 153 drug-resistant tuberculosis patients(resistant group),167 non drug resistant tuberculosis patients(non-resistant group),and 120 patients without abnormal pulmonary examination(control group)selected.According to the drug resistance,the resistant group was divided into multi-drug resistant group(112 cases)and extensive drug resistance group(41 cases).The expression of miR-431 and Notch2 in bronchoalveolar lavage fluid were detected by fluorescence real-time quantitative polymerase chain reaction(qRT-PCR).The correlations between the expression of miR-431,Notch2 and the clinicopathological characteristics of patients in drug resistant group were analyzed using Spearman analysis;and multivariate logistic regression was used to analyze the factors influencing drug resistance of TB patients.Results The expression of miR-431 and Notch2 in bronchoalveolar lavage fluid of control group,non-resistant group and resistant group were significantly different(P<0.05).The expression of miR-431 in bronchoalveolar lavage fluid of the non-resistant group and the resistant group was significantly higher than that in the control group(P<0.05),and the expression of Notch2 was significantly lower(P<0.05).The expression of miR-431 in bronchoalveolar lavage fluid of resistant group was significantly higher than that of non-resistant group(P<0.05),and the expression of Notch2 was significantly lower(P<0.05).The expression of miR-431 in bronchoalveolar lavage fluid of extensive drug resistance group was significantly higher than that of multi drug resistant group(P<0.05),and the expression of Notch2 was significantly lower(P<0.05).The expression of miR-431 and Notch2 was not correlated to gender or tuberculous cavity(P>0.05),but significantly correlated to age,smoking history,drug resistance and lung field occupied by lesions(P<0.05).Spearman analysis showed that the expression of mir-431 and Notch2 in bronchoalveolar lavage fluid was significantly negatively correlated(P<0.05).The results of multivariate logistic regression analysis showed that lung field occupied by lesions>3,high expression of miR-431 were all risk factors of drug resistance(P<0.05),and high expression of Notch2 was an independent protective factor(P<0.05).Conclusion MiR-431 and Notch2 may be involved in the formation of drug resistance in patients with pulmonary tuberculosis and may become clinical biomarkers.