急性呼吸窘迫综合征患者外周血单核细胞中肿瘤坏死因子-α诱导蛋白8样分子2的表达与病情程度相关

Study of tumor necrosis factor-α induced protein 8 like-2 expression in peripheral blood mononuclear cells of patients with acute respiratory distress syndrome correlate with disease severity

【摘要】目的探讨肿瘤坏死因子-α诱导蛋白8样分子2（TIPE2）是否参与了急性呼吸窘迫综合征（ARDS）的发病过程及其机制。方法采用前瞻性观察性研究方法，选择2013年7月至2015年7月解放军总医院急诊科收治的39例ARDS患者为研究对象，以同期35例健康体检者作为健康对照组。记录患者入院24h内急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分、血气分析、降钙素原（PCT）和C-反应蛋白（CRP）。采用实时定量反转录-聚合酶链反应（RT—PCR）检测外周血单核细胞（PBMC）中TIPE2和血浆黏病毒抗性蛋白1（MX1）的mRNA表达，采用Spearman等级分析各指标之间的相关性。结果39例ARDS患者入院24h内APACHEⅡ评分平均为（25±3）分，PCT平均为（1．85±0．41）μg/L，CRP平均为（18．0±3．0）mg／L。ARDS组PBMC中TIPE2mRNA表达水平显著低于健康对照组（2^△△Ct：3．28±0．15比8．87±0．20，P〈0．001），而血浆MX-1mRNA表达水平显著高于健康对照组（2^△△Ct：39．44±0．46比20．10±0．32，P〈0．001）。相关分析结果显示：TIPE2mRNA与MX1mRNA表达水平呈显著负相关（r=-0．630，P〈0．001），与APACHEⅡ评分也呈显著负相关（r=-0．781，P〈0．001），而与PCT、CRP均无显著相关性（r值分别为0．143、0．330，均P〉0．05）；MX1mRNA表达水平与APACHEⅡ评分呈显著正相关（r=0．893，P〈0．001），而与PCT、CRP无显著相关性（r值分别为0．230、0．210，均P〉0．05）。结论ARDS患者存在TIPE2表达下调，并与病情严重程度呈负相关；提示TIPE2可能参与了ARDS的发病过程。

Objective To demonstrate the effect of tumor necrosis factor-α induced protein 8 like-2 （TIPE2） expression in patients with acute respiratory distress syndrome （ARDS） and its mechanism. Methods A prospective observation was conducted. Thirty-nine patients with ARDS admitted to department of emergency of PLA General Hospital from July 2013 to July 2015 were enrolled, and 35 healthy persons served as control group. The acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ ） score within 24 hours after admission, blood gas analysis, procalcitonin （PCT）, and C-reactive protein （CRP） were recorded. The mRNA expressions of TIPE2 in peripheral blood mononuclear cell （PBMC） and myxoma resistance protein 1 （MX1） in plasma were determined by real-time quantitative reverse transeription-polymerase chain reaction （RT-PCR）. The correlations were analyzed by Spearman rank correlation analysis. Results The mean of APACHE Ⅱ score in 39 patients with ARDS was 25 ± 3, the mean of PCT was （1.85 ± 0.41） μg/L, and the mean of CRP was （18.0 ± 3.0） μg/L. The TIPE2 mRNA expression in PBMC ofARDS patients was significantly down-regulated as compared with that of healthy control group （2^△△Ct： 3.28 ± 0.15 vs. 8.87 ± 0.20, P 〈 0.001）, and the MX-1 mRNA expression in plasma was significantly higher than that of healthy control group （2^△△Ct： 39.44±0.46 vs. 20.10±0.32, P 〈 0.001）. It was shown by correlation analysis results that the TIPE2 mRNA expression was negatively correlated with MX1 mRNA expression （r = -0.630, P 〈 0.001）, so as APACHE Ⅱ score （r = -0.781, P 〈 0.001）, but no correlation was found between TIPE2 mRNA and PCT as well as CRP （r value was 0.143 and 0.330, respectively, both P 〉 0.05）. The MX1 mRNA expression was positively correlated with APACHE Ⅱ seore （r = 0.893, P 〈 0.001）, but no correlation was found between MX1 mRNA and PCT as well as CRP （r value was 0.230 and 0.210, respectively, both P 〉 0.05）. Conclusion TIPE2 expression was decreased in ARDS patients, which negatively correlate with disease severity, and indicate TIPE2 might be involved in the pathogenic process of ARDS.