急性呼吸窘迫综合征患者香叶基香叶基焦磷酸合成酶的表达及其临床意义

Clinical significance of geranylgeranyl diphosphate synthase expression levels in patients with acute respiratory distress syndrome

目的·通过检测急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)患者外周血单个核细胞中香叶基香叶基焦磷酸合成酶(geranylgeranyl diphosphate synthase,GGPPS)的表达情况,研究GGPPS在ARDS诊治中的临床意义。方法·通过定量反转录聚合酶链反应检测ARDS患者(ARDS组)和正常人群(对照组)外周血单个核细胞中GGPPS mRNA水平,采用蛋白质印迹法(Western blotting)检测ARDS组和对照组外周血单个核细胞中GGPPS蛋白表达水平。同时比较ARDS存活组和死亡组GGPPS的表达差异,并采用Spearman相关分析明确GGPPS表达与ARDS患者临床指标的相关性。结果·ARDS组外周血单个核细胞中GGPPS mRNA水平明显高于对照组(P=0.000),并且随ARDS病情加重逐渐升高(P<0.05)。ARDS组外周血单个核细胞中GGPPS蛋白表达明显高于对照组(P<0.05),并且随病情加重逐渐升高(P<0.05)。ARDS死亡组外周血单个核细胞中GGPPS mRNA水平及蛋白表达水平高于ARDS存活组(P<0.05)。ARDS患者外周血单个核细胞中GGPPS mRNA高表达与高的急性生理与慢性健康评分Ⅱ(APACHE Ⅱ)(r=0.862,P=0.000)、高序贯器官功能衰竭估计(SOFA)评分(r=0.719,P=0.023)、低氧合指数(r=-0.821,P=0.000)、高C反应蛋白(r=0.758,P=0.024)及高白细胞计数(r=0.761,P=0.015)相关。结论·ARDS患者外周血单个核细胞中GGPPS表达水平升高,且其表达水平与ARDS病情严重程度及预后相关,GGPPS有望成为ARDS病情严重程度评估的生物标志物。

Objective·To investigate the clinical significance of geranylgeranyl diphosphate synthase(GGPPS)by detecting its expression levels in the peripheral blood mononuclear cells of patients with acute respiratory distress syndrome(ARDS).Methods·The GGPPS mRNA expression levels in peripheral blood mononuclear cells of patients with ARDS were compared with those of healthy controls,by using quantitative reverse-transcription polymerase chain reaction.The GGPPS protein expression levels in the peripheral blood mononuclear cells were detected by Western blotting.The differential expression of GGPPS in survivors and non-survivors of ARDS was also examined.The correlations between GGPPS and clinical indicators of ARDS were tested by using Spearman’s coefficients.Results·The mRNA and protein expression levels of GGPPS in the peripheral blood mononuclear cells of patients with ARDS were significantly higher than those of healthy controls(P<0.05),and these levels increased with the aggravation of ARDS(P<0.05).Moreover,the expression levels of GGPPS mRNA and protein were significantly higher in the patients who succumbed to ARDS than those in the survivors(P<0.05).The elevated level of GGPPS mRNA was correlated with the elevated acute physiology and chronic health evaluationⅡ(APACHEⅡ)score(r=0.862,P=0.000),elevated sequential organ failure assessment(SOFA)score(r=0.719,P=0.023),lower oxygenation index(r=-0.821,P=0.000),elevated C-reactive protein(r=0.758,P=0.024),and elevated white blood cells(r=0.761,P=0.015).Conclusion·The elevated expression level of GGPPS in the peripheral blood mononuclear cells is associated with greater disease severity and poorer prognosis in patients with ARDS.Based on these observations,GGPPS is expected to serve as an appropriate biomarker to assess the severity of ARDS.