支气管肺发育不良早产儿血清生长分化因子11、血管粘附蛋白1水平变化和临床意义

Changes in serum growth differentiation factor 11 and vascular adhesion protein 1 levels and clinical significance in preterm infants with bronchopulmonary dysplasia

摘要

目的 探讨支气管肺发育不良(BPD)组和非BPD组早产儿血清生长分化因子11(GDF11)、血管粘附蛋白1(VAPＧ1)的水平变化,探究其临床意义。方法 选取2019年1月至2023年1月在江苏省苏北人民医院新生儿科收住入院胎龄＜32周的102例早产儿作为研究对象,按照BPD诊断标准将其分为BPD组(62例)和非BPD组(40例);将BPD组再分为轻度BPD组(38例)和中重度BPD组(24例),比较不同组别生后第1天、7天、14天血清GDF11、VAPＧ1水平,以受试者工作特征(ROC)曲线评估血清GDF11、VAPＧ1水平对BPD的早期预测价值,采用Pearson相关性分析评估血清GDF11、VAPＧ1水平与早产儿BPD严重程度的相关性。结果 BPD组早产儿生后第7天、第14天的血清GDF11水平均低于非BPD组,差异有统计学意义(t值分别为-4．561、-5．319,P＜0．05);BPD组早产儿血清GDF11水平随出生日龄延长呈下降趋势,差异有统计学意义(F＝25．139,P＜0．05);BPD组早产儿生后第7天、第14天的血清VAPＧ1水平均高于非BPD组,差异有统计学意义(t值分别为4．297、3．665,P＜0．05);BPD组早产儿血清VAPＧ1水平随出生日龄延长逐渐升高,差异有统计学意义(F＝15．321,P＜0．05);血清GDF11及VAPＧ1水平于生后第7天、第14天预测BPD发生的曲线下面积(AUC)均大于0．7,两因子联合检测的AUC分别为0．803、0．856,均高于单独检测;轻度BPD组生后第7天、第14天血清GDF11水平高于中重度BPD组,差异均有统计学意义(t值分别为5．180、7．581,P＜0．05);轻度BPD组生后第7天、第14天血清VAPＧ1水平均低于中重度BPD,差异有统计学意义(t值分别为-4．281、-2．841,P＜0．05);血清GDF11水平与早产儿BPD的严重程度呈负相关性(r＝-0．617,P＜0．01);血清VAPＧ1水平与早产儿BPD的严重程度呈正相关性(r＝0．400,P＜0．01)。结论 血清GDF11、VAPＧ1水平均可作为早期预测早产儿BPD发生及病情评估的指标,具有一定的临床指导价值.

Abstract

Objective To investigate the changes in serum growth differentiation factor 11 (GDF11) and vascular adhesion protein 1 (VAPＧ1) levels in preterm infants in bronchopulmonary dysplasia (BPD) group and non-BPD group, and to explore their clinical significance. Methods A total of 102 premature infants with gestational age ＜32 weeks admitted to the Department of Neonatology of Jiangsu Subei People's Hospital from January 10, 2019 to January 10, 2023 were selected as the study subjects, and were divided into BPD group (62 cases) and non-BPD group (40 cases) according to the diagnostic criteria for BPD. BPD group was further divided into mild BPD group (38 cases) and moderate to severe BPD group (24 cases). Serum GDF11 and VAPＧ1 levels of different groups were compared on day 1, day 7 and day 14, and the early predictive value of serum GDF11 and VAPＧ1 levels on BPD was evaluated by receiver operating characteristic (ROC) curve. Pearson correlation analysis was used to evaluate the correlation between serum GDF11 and VAPＧ1 levels and the severity of BPD in preterm infants. Results The serum GDF11 level in the BPD group was lower than that in the non-BPD group on day 7 and day 14 after birth, and the difference was statistically significant (t value was -4．561 and -5．319, P＜0．05). The serum GDF11 level of preterm infants in BPD group decreased with the extension of birth age, and the difference was statistically significant (F＝25．139, P＜0．05). The serum VAPＧ1 level in BPD group was higher than that in non-BPD group on day 7 and day 14 after birth, and the difference was statistically significant (t value was 4．297 and 3．665, P＜0．05). The serum VAPＧ1 level of preterm infants in BPD group increased gradually with the extension of birth age, and the difference was statistically significant (F＝15．321, P＜0．05). The area under the curve (AUC) of serum GDF11 and VAPＧ1 levels predicted the occurrence of BPD on day 7 and day 14 after birth was greater than 0．7, and the AUC of the combined detection of the two factors was 0．803 and 0．856, respectively, which were higher than those of the single test. The serum GDF11 level in mild BPD group was higher than that in moderate and severe BPD group on day 7 and day 14 after birth, and the differences were statistically significant (t value was 5．180 and 7．581, P＜0．05). The serum VAPＧ1 level of mild BPD group was lower than that of moderate and severe BPD group on day 7 and day 14 after birth, and the difference was statistically significant (t value was -4．281 and -2．841, P＜0．05). Serum GDF11 level was negatively correlated with the severity of BPD in preterm infants (r＝-0．617, P＜0．01). Serum VAPＧ1 level was positively correlated with the severity of BPD in preterm infants (r＝0．400, P＜0．01). Conclusion Serum levels of GDF11 and VAPＧ1 can be used as indicators for early prediction of the occurrence and evaluation of BPD in preterm infants, and have certain clinical guiding value.

关键词

早产儿 / 支气管肺发育不良 / 生长分化因子11 / 血管粘附蛋白Ｇ1 / 预测

Key words

preterm infants / bronchopulmonary dysplasia / growth differentiation factor 11 / vascular adhesion protein-Ｇ1 / prediction

参考文献

[1] [1] 鲁元元, 方欣, 赵小林, 等 ． 新生儿支气管肺发育不良高危因素的研究进展[J]． 中国妇幼健康研究,2020,31(12):1739-1743．

[2] [2] Schmidt A R, Ramamoorthy C. Bronchopulmonary dysplasia[J]. Paediatr Anaesth, 2022, 32(2): 74-180.

[3] [3] Wang W, Qu R, Wang X, et al. GDF11 antagonizes psoriasis-like skin inflammation via suppression of NF-κB signaling pathway[J]. Inflammation, 2019, 42(1): 319-330.

[4] [4] Suto H, Nambu A, Morita H, et al. IL-25 enhances T(H)17 cell-mediated contact dermatitis by promoting IL-1β production by dermal dendritic cells[J]. J Allergy Clin Immunol, 2018, 142(5): 1500-1509.

[5] [5] 何莎莎, 董文斌 ． 细胞因子在早产儿BPD发病机制中的作用[J]． 中国妇幼健康研究,2021,32(4):619-625．

[6] [6] 邵肖梅, 叶鸿瑁, 邱小汕 ． 实用新生儿学[M]．第5版． 北京: 人民卫生出版社,2021:596-601．

[7] [7] Yu X, Chen X, Zheng X D, et al. Growth differentiation factor 11 promotes abnormal proliferation and angiogenesis of pulmonary artery endothelial cells[J]. Hypertension, 2018, 71(4): 729-741.

[8] [8] Yung L M, Yang P, Joshi S, et al. ACTRIIA-Fc rebalances activin/GDF versus BMP signaling in pulmonary hypertension[J]. Sci Transl Med, 2020, 12(543): eaaz5660.

[9] [9] Xu H B, Qin B, Zhang J, et al. Growth differentiation factor 11 relieves acute lung injury in mice by inhibiting inflammation and apoptosis[J]. Eur Rev Med Pharmacol Sci, 2020, 24(12): 6908-6918.

[10] [10] Wang J, Hu K, Cai X, et al. Targeting PI3K/AKT signalling for treatment of idiopathic pulmonary fibrosis[J]. Acta Pharm Sin B, 2022, 12(1): 18-32.

[11] [11] Sun Y, Zhang Y, Chi P. Pirfenidone suppresses TGF-β1-induced human intestinal fibroblasts activities by regulating proliferation and apoptosis via the inhibition of the Smad and PI3K/AKT signaling pathway[J]. Mol Med Rep, 2018, 18(4): 3907-3913.

[12] [12] Suto H, Nambu A, Morita H, et al. IL-25 enhances T(H)17 cell-mediated contact dermatitis by promoting IL-1β production by dermal dendritic cells[J]. J Allergy Clin Immunol, 2018, 142(5): 1500-1509.

[13] [13] Frohlich J, Vinciguerra M. Candidate rejuvenating factor GDF11 and tissue fibrosis: friend or foe? [J]. Geroscience, 2020, 42(6): 1475-1498.

[14] [14] Bournazou E, Samuels J, Zhou H, et al. Vascular adhesion parotein-1 (VAP-1) as predictor of radiographic severity in symptomatic knee osteoarthritis in the New York University Cohort[J]. Int J Mol Sci, 2019, 20(11): 2642.

基金资助

江苏省妇幼健康科研项目(F202152)