摘要目的 探讨支气管肺发育不良(bronchopulmonary dysplasia,BPD)患儿生后36 h内及生后第3周血液代谢物特征性变化,为BPD的诊断提供新的生物标记物. 方法 收集2014年1月至2016年10月在中山大学附属第六医院住院的胎龄＜ 32周的BPD早产儿为BPD组,匹配同期住院、胎龄相差1周以内的非BPD早产儿为对照组.于生后36 h及第3周,采取足跟末梢血,制备血片,利用液相色谱-串联质谱联用技术进行代谢产物测定,并用正交偏最小二乘判别分析法(orthogonal partial least squares discriminant analysis,OPLS-DA)对数据进行分析.采用x2检验(或Fisher精确概率法)、Mann-Whitney U检验或t检验对数据进行统计学分析. 结果 (1) BPD组和对照组于生后36h内和第3周时各分别有20例和11例患儿.BPD组患儿胎膜早破时间、平均住院时间、无创和有创机械通气时间,以及住院期间总用氧时间均高于对照组[M(P25～P75)或((x)±s),13.5(0.0～98.3)与0.0 (0.0～0.0)h,Z=3.049;(66.6±20.5)与(43.9±9.3)d,t=4.574;267.0 (199.5～516.1)与110.5 (0.0～238.5)h,Z=-3.428;117.5 (0.0～269.3)与0.0 (0.0～72.0)h,Z=-2.785;1 184.0±386.6与(595.9±270.3)h,t=5.576;P值均＜0.05],其余一般情况差异无统计学意义.(2)生后36 h内,BPD组患儿血甘氨酸、脯氨酸、色氨酸、胡椒酰胺水平较对照组降低[(201.59±65.01)与(290.90±137.56)μmol/L,t=-2.625;103.55(72.43～434.57)与439.48(103.80～608.98)μmol/L,Z=-2.245;29.54(20.30～41.04)与47.42(29.46～73.57)μmol/L,Z=-2.326;50.04(35.29～104.78)与95.79 (76.21～129.97) μmol/L,Z=-2.029],血谷氨酸水平高于对照组[(224.30±67.40)与(182.67±40.87)μmol/L,t=2.362](P值均＜ 0.05).(3)出生第3周,BPD组血甘氨酸、色氨酸、脯氨酸水平低于对照组[分别为(185.92±61.51)与(271.85±115.85)μmol/L,t=-2.177;(39.41±18.22)与(63.92±17.50)μmol/L,t=-3.217;90.23(37.93～146.37)与330.15 (47.79～622.90) μmol/L,Z=-2.134],鸟氨酸水平高于对照组[(75.09±43.21)与(39.25±16.53)μmol/L,t=2.569](P值均＜0.05).结论 血代谢产物甘氨酸、脯氨酸、色氨酸等代谢产物在BPD早期诊断中可能具有潜在的应用价值.

abstractsObjective To analyze the changes in blood metabolites in premature infants with bronchopulmonary dysplasia (BPD) within 36 h and in the 3rd week after birth in order to find new biomarkers for diagnosis of BPD.Methods The BPD group included 20 premature infants (＜32 gestational weeks) hospitalized in the Neonatal Intensive Care Unit (NICU) of the Sixth Affiliated Hospital of Sun Yat-sen University and diagnosed with BPD from January 2014 to October 2016.Another 20 non-BPD premature infants with similar gestational age (within one week) who were admitted during the same period were enrolled in the control group.Blood samples of both groups were collected within 36 h and in the 3rd week after birth.Liquid chromatography-tandem mass spectrometry was used to detect blood metabolites and the obtained data were subjected to metabolomics analysis using orthogonal partial least squares discriminant analysis.Chi-square test (or Fisher's exact test),Mann-Whitney U test or t test was used for statistical analysis.Results (1) Twenty and 11 blood samples were collected within 36 h and in the 3rd week after birth from the BPD and the control group,respectively.Compared with the control group,the interval between premature rupture of membranes and delivery,the average length of hospital stay,non-invasive and invasive mechanical ventilation duration and the total duration of supplemental oxygen during hospitalization in the BPD group were longer [M (P25-P75) or ((x)±s):13.5 (0.0-98.3) vs 0.0 (0.0-0.0) h,Z=3.049;(66.6±20.5) vs (43.9±9.3) d,t=4.574;267.0 (199.5-516.1) vs 110.5 (0.0-238.5) h,Z=-3.428;117.5 (0.0-269.3) vs 0.0 (0.0-72.0) h,Z=-2.785;(1 184.0±386.6) vs (595.9±270.3) h,t=5.576;all P＜0.05].(2) Within 36 h after birth,the levels of glycine,proline,tryptophan and piperamide-C5:1 in the BPD group were decreased obviously compared with those in the control group [(201.59±65.01) vs (290.90± 137.56) μmol/L,t=-2.625;103.55 (72.43-434.57) vs 439.48 (103.80-608.98) μ mol/L,Z=-2.245;29.54 (20.30-41.04) vs 47.42 (29.46-73.57) μ mol/L,Z=-2.326;50.04 (35.29-104.78) vs 95.79 (76.21-129.97) μmol/L,Z=-2.029;all P＜0.05].However,the glutamate level was increased [(224.30±67.40) vs (182.67±40.87) μmol/L,t=2.362,P＜0.05].(3) In the 3rd week after birth,the levels of glycine,proline and tryptophan in the BPD group were lower compared to those in the control group [(185.92±61.51) vs (271.85± 115.85) μmol/L,t=-2.177;(39.41± 18.22) vs (63.92± 17.50) μ mol/L,t=-3.217;90.23 (37.93-146.37) vs 330.15 (47.79-622.90) μ mol/L,Z=-2.134;all P＜0.05].However,the ornithine level was higher [(75.09± 43.21) vs (39.25 ± 16.53) μ mol/L,t=2.569,P＜0.05].Conclusions Glycine,proline and tryptophan in blood are potential biomarkers for early diagnosis of BPD.