重症肺炎患儿血清 FSTL1、Ang-1、8-OHdG 表达与急性呼吸窘迫综合征发生的关系

Relationships of expression levels of FSTL1, Ang-1 and 8-OHdG in serum with occurrence of acute respiratory distress syndrome in children with severe pneumonia

摘要

目的 探究重症肺炎(SP)患儿血清卵泡抑素样蛋白1(FSTL1)、血管生成素-1(Ang-1)、8-羟基脱氧鸟苷(8-OHdG)表达与急性呼吸窘迫综合征(ARDS)发生的关系。方法 选取2021年1月至2024年1月电子科技大学医学院附属妇女儿童医院/成都市妇女儿童中心医院收治的189例SP患儿为研究对象,根据治疗期间是否发生ARDS将189例SP患儿分为SP合并ARDS患儿(n=104)和单纯SP患儿(n=85),分别纳入研究组和对照组,采用酶联免疫吸附试验(ELISA)法检测SP患儿血清FSTL1、Ang-1、8-OHdG表达水平;采用Spearman法分析FSTL1、Ang-1、8-OHdG水平与临床肺部感染评分(CPIS)、慢性健康状况评分系统Ⅱ(APACHEⅡ)的相关性;采用多因素Logistic分析SP患儿发生ARDS的影响因素;采用受试者工作特征(ROC)曲线评估FSTL1、Ang-1、8-OHdG水平预测SP患儿发生ARDS的价值。结果 研究组的氧合指数、血小板计数(PLT)、血红蛋白(Hb)的数值低于对照组,CPIS评分、APACHEⅡ评分、白细胞计数(WBC)、C反应蛋白(CRP)的数值高于对照组(t=5.507、5.481、2.179、6.861、12.003、2.389、3.563,P<0.05)。研究组血清FSTL1、8-OHdG的表达水平高于对照组,Ang-1的表达水平低于对照组(t=7.569、4.832、7.427,P<0.001)。研究组患儿血清FSTL1、8-OHdG水平与CPIS和APACHEⅡ评分呈正相关(r_s=0.684、0.557、0.637、0.582,P<0.001),Ang-1水平与CPIS和APACHEⅡ评分呈负相关(r_s=-0.712、-0.665,P<0.001)。FSTL1、8-OHdG水平为SP患儿发生ARDS的危险因素[OR=4.539(95%CI:2.424~8.499)、3.945(95%CI:2.279~6.829),P<0.05],氧合指数、Ang-1水平为SP患儿发生ARDS的保护因素[OR=0.448(95%CI:0.226~0.890)、0.385(95%CI:0.231~0.641),P<0.05]。FSTL1、Ang-1、8-OHdG水平预测SP患儿发生ARDS的曲线下面积(AUC)分别为0.779、0.803、0.721,当三者联合预测SP患儿发生ARDS的AUC增大至0.887时,三者联合预测SP患儿发生ARDS的价值,优于FSTL1(Z=2.559,P<0.05)、Ang-1(Z=1.990,P<0.05)、8-OHdG(Z=3.717,P<0.05)单一预测的价值。结论 重症肺炎患儿血清FSTL1、8-OHdG水平升高,Ang-1水平下降与ARDS的发生密切相关,三者联合预测重症肺炎患儿发生急性呼吸窘迫综合征的价值较高。

Abstract

Objective To investigate relationships of expression levels of follostatin-like-protein1 (FSTL1), angiopoietin-1 (Ang-1) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in serum with occurrence of acute respiratory distress syndrome (ARDS) in children with severe pneumonia (SP). Methods 189 children with SP who admitted to our hospital from January 2021 to January 2024 were selected as research subjects. According to whether ARDS occurred during treatment period, the children with SP were divided into SP complicated with ARDS group (study group, n=104) and simple SP group (control group, n=85). Enzyme linked immunosorbent assay (ELISA) was applied to detect expression levels of serum FSTL1, Ang-1 and 8-OHdG of the children with SP. Spearman correlation analysis was applied to analyze correlations of serum FSTL1, Ang-1 and 8-OHdG levels with clinical pulmonary infection score (CPIS) and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score. Multivariate Logistic regression analysis was applied to analyze influencing factors of ARDS in children with SP. Receiver operating characteristic (ROC) curve was drawn to evaluate value of FSTL1, Ang-1, and 8-OHdG levels for predicting occurrence of ARDS in children with SP. Results The levels of oxygenation index, platelet (PLT) and haemoglobin (Hb) in the study group were lower than those in the control group, while the CPIS score, APACHE Ⅱ score, white blood cell count (WBC) and C-reactive protein (CRP) level were higher than those in the control group (t=5.507, 5.481, 2.179, 6.861, 12.003, 2.389 and 3.563 respectively, all P<0.05). The expression levels of serum FSTL1 and 8-OHdG in the study group were higher than those in the control group, while expression level of Ang-1 was lower than that in the control group (t=7.569, 4.832, 7.427, P<0.001). The serum levels of FSTL1 and 8-OHdG in the study group were positively correlated with CPIS and APACHE Ⅱ scores (r_s=0.684, 0.557, 0.637 and 0.582 respectively, all P<0.001), while Ang-1 level was negatively correlated with CPIS and APACHE Ⅱ scores (r_s=-0.712, and -0.665 respectively, both P<0.001). The serum levels of FSTL1 and 8-OHdG were risk factors for ARDS in children with SP (OR=4.539, 95%CI:2.424-8.499; OR=3.945, 95%CI:2.279-6.829, both P<0.05), while oxygenation index and Ang-1 levels were protective factors for ARDS in children with SP (OR=0.448, 95%CI:0.226-0.890; OR=0.385, 95%CI:0.231-0.641, both P<0.05). The areas under the curve (AUCs) of serum FSTL1, Ang-1 and 8-OHdG levels for predicting ARDS in children with SP were 0.779, 0.803 and 0.721 respectively. The AUC of the combination of the three indexes for predicting ARDS was 0.887, showing that the AUC of the joint prediction for ARDS in children with SP was greater than that of single FSTL1 prediction (Z=2.559, P<0.05), single Ang-1 prediction (Z=1.990, P<0.05) and single 8-OHdG prediction (Z=3.717, P<0.05) alone. Conclusion The elevated serum levels of FSTL1 and 8-OHdG, and the lowered serum level of Ang-1 are closely related to occurrence of ARDS in children with SP. The combined prediction of these three indexes has high predictive value for occurrence of ARDS in children with SP.

关键词

儿童 / 重症肺炎 / 血清卵泡抑素样蛋白1 / 血管生成素-1 / 8-羟基脱氧鸟苷 / 急性呼吸窘迫综合征

Key words

children / severe pneumonia / follostatin-like-protein1 / angiopoietin-1 / 8-hydroxy-2'-deoxyguanosine / acute respiratory distress syndrome

参考文献

[1] Vadász I, Husain-Syed F, Dorfmüller P, et al. Severe organizing pneumonia following COVID-19[J]. Thorax, 2021, 76(2): 201-204.

[2] 杨丽莎, 王艳平, 李淑娇, 等. NLR、D-D、MLR评估重症肺炎患者病情严重程度及预后的价值[J]. 分子诊断与治疗杂志, 2023, 15(7): 1203-1206+1211.

[3] 宋丹, 许蕊. 特发性肺纤维化患者血清FSTL1、Syndecan-1与肺功能和预后的关系[J]. 检验医学与临床, 2024, 21(4): 450-454.

[4] Zhang M, Huang X, Song Y, et al. Astragalus propinquus schischkin and Salvia miltiorrhiza bunge promote angiogenesis to treat myocardial ischemia via Ang-1/Tie-2/FAK pathway[J]. Front Pharmacol, 2023, 13: 110-117.

[5] 金珍杰, 何平. HBV相关性肾炎患者肾组织氧化应激指标SOD、HO-1、8-OHdG的表达及临床意义[J]. 浙江医学, 2023, 45(5): 483-486, 563.

[6] 葛均波, 王辰, 王健安. 内科学[M].10版. 北京: 人民卫生出版社, 2024: 46-49.

[7] 乔莉, 马元, 张劲松. 急性呼吸窘迫综合征:柏林标准[J]. 中华急诊医学杂志, 2012, 21(9): 952-957.

[8] 王忆梅, 张宇成, 朱怡栋, 等. 中医“肺肠合治”法联合双歧杆菌活菌胶囊在重症肺炎合并胃肠功能障碍患者中的应用效果[J]. 检验医学与临床, 2025, 22(1): 76-80.

[9] 张鸥, 周祥林, 吴萍, 等. 血清NGAL水平联合APACHEⅡ评分对重症肺炎并发急性肾损伤患者预后的预测价值[J]. 广西医学, 2024, 46(4): 495-500.

[10] Lee K L, Lee C M, Yang T L, et al. Severe Mycoplasma pneumoniae pneumonia requiring intensive care in children, 2010-2019[J]. J Formos Med Assoc, 2021, 120(1): 281-291.

[11] Tsai T A, Tsai C K, Kuo K C, et al. Rational stepwise approach for Mycoplasma pneumoniae pneumonia in children[J]. J Microbiol Immunol Infect, 2021, 54(4): 557-565.

[12] 蔡剑英, 陶学芳, 王国文, 等. 重症肺炎患者血清IL-17及IL-12P70与CD64表达水平及其与预后的关系[J]. 中华医院感染学杂志, 2024,(16): 2452-2456.

[13] Du R, Li K, Guo K, et al. FSTL1: A double-edged sword in cancer development[J]. Gene, 2024, 906(3): 148263-148273.

[14] Sun W, Yang X, Chen L, et al. FSTL1 promotes alveolar epithelial cell aging and worsens pulmonary fibrosis by affecting SENP1-mediated deSUMOylation[J]. Cell Biol Int, 2023, 47(10): 1716-1727.

[15] Zhang Y, Yan L, Yang J, et al. Silencing of FSTL1 alleviated LPS-induced inflammatory damage and oxidative damage in human bronchial epithelial cells via BMP4/KLF4 axis[J]. Int Arch Allergy Immunol, 2022, 183(7): 785-795.

[16] Wang Y, Zhang D, Liu T, et al. FSTL1 aggravates OVA-induced inflammatory responses by activating the NLRP3/IL-1β signaling pathway in mice and macrophages[J]. Inflamm Res, 2021, 70(7): 777-787.

[17] 屈菊梅, 冯成虎, 曹贝贝. 急性呼吸窘迫综合征新生儿血清LncRNA NEAT1、miR-129-5p水平与病情程度及预后的关系[J]. 中国妇幼健康研究, 2025, 36(5): 31-37.

[18] Li Q, Chen Y, Lin L. Value of serum miR-34a and Ang-1 in severity evaluation and prognosis of neonatal respiratory distress syndrome[J]. Emerg Med Int, 2022, 5(1): 5480026-5480031.

[19] 孙灿光, 张弦, 颜晓磊, 等. Ang-1和MCP-1在小儿支气管哮喘外周血中的表达及其与肺功能的关系[J]. 河南医学研究, 2024, 33(5): 885-888.

[20] Liu P, Ryczko M, Xie X, et al. New soluble angiopoietin analog of Hepta-ANG1 prevents pathological vascular leakage[J]. Biotechnology and Bioengineering, 2021, 118(1): 423-432.

[21] 王慧娟, 张高丽, 张冬娇, 等. 尘肺病患者血清8-羟基脱氧鸟苷表达水平和临床意义[J]. 医药论坛杂志, 2024, 45(4): 395-398, 403.

[22] Cao P, Zhang C, Hua D X, et al. Serum 8-Hydroxy-2'-deoxyguanosine predicts severity and prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease[J]. Lung, 2022, 200(1): 31-39.

[23] Cao L F, Cheng J Y, Xu Z, et al. Serum 8-hydroxydeoxyguanosine is a potential indicator for the severity and prognosis in patients with community-acquired pneumonia: a prospective cohort study[J]. J Immunol, 2022, 208(2): 321-327.

[24] 吕月华, 赵丽, 李婷. 重症肺炎患儿临床特征及影响患儿预后的危险因素分析[J]. 实用预防医学, 2024, 31(3): 314-318.

基金资助

成都市卫生健康委员会科研课题(2021107)