血清RAGE、HMGB1水平与重症肺炎急性呼吸窘迫综合征发病及IFN⁃γ/IL⁃4变化的关系

doi:10.3969/j.issn.1006-5725.2024.04.013

Abstract

Abstract:

Objective To explore the correlation between the expression level of serum Receptor for Advanced Glycation End?Product （RAGE） and High?Mobility Group Protein B1 （HMGB1） expression with the occurrence of acute respiratory distress syndrome （ARDS） and interferon?γ/interleukin?4 （IFN?γ/IL?4） ratio in patients with severe pneumonia （SP）. Methods A prospective investigation was carried out on one hundred children with SP admitted to our hospital from March 2020 to February 2022， and the participants were classified into ARDS group （n = 56） and control group （n = 44） based on the occurrence of secondary ARDS. General informations werecollected. The expression of RAGE， HMGB1， IFN?γ and IL?4 in peripheral blood was measured using Enzyme?Linked Immunosorbent Assay （ELISA）. Then multivariate Logistic regression analysis was conducted to screen the influencing factors of secondary ARDS in SP children， and the correlation with IFN?γ/IL?4 ratio was verified by pearson correlation analysis， moreover， receiver operating characteristic （ROC） curve was plotted to evaluate the value of RAGE and HMGB1 expression in predicting the occurrence of ARDS in SP children. Results There were no statistical difference in gender， age， body temperature and onset season between the two SP groups. The ARDS group had more types of pathogenic bacteria， larger ratio of the partial pressure of oxygen in arterial blood to the inspired oxygen fraction （PaO₂/FiO₂）， higher Acute Physiological Score （APS）， and up?regulated expression of RAGE， HMGB1， IFN?γ and IL?4， as well as larger IFN?γ/IL?4 ratio than those of control group， with statistical difference （all P < 0.05）. Multivariate Logistic regression analysis revealed that pathogen type， PaO₂/FiO₂ ratio， RAGE， HMGB1， IFN?γ， IL?4 and IFN?γ/IL?4 were the influencing factors for the occurrence of ARDS in children with SP. Pearson correlation test denoted that the serum RAGE and HMGB1 expression levels of SP children were positively correlated with IFN?γ， IL?4 and IFN?γ/IL?4 ratio （P < 0.05）. ROC curve found that the AUC of serum RAGE and HMGB1 in predicting the occurrence of ARDS in SP children was 0.707 and 0.750， with a sensitivity of 73.2% and 64.3%， and a specificity of 68.2% and 77.3%. The combined test of RAGE and HMGB1 in predicting the occurrence of ARDS in SP children reached an AUC of 0.848， providing a sensitivity and specificity of 80.4% and 81.8% respectively. Conclusions Serum RAGE and HMGB1 expression levels are elevated in SP children with ARDS， and the two are positively correlated with IFN?γ/IL?4 ratio. Therefore， monitoring serum RAGE and HMGB1 expression in children with ARDS secondary to SP has predictive value for the risk of ARDS in SP children.

Key words: receptor for advanced glycation end?product, high?mobility group protein b1, severe pneumonia, acute respiratory distress syndrome, IFN-γ, IL-4

CLC Number:

R563

Jingcai WANG,Chunyan GUO,Lixin YANG,Xiaoqing. JING. Correlation of serum RAGE and HMGB1 expression with the occurrence of acute respiratory distress syndrome and IFN⁃γ/IL⁃4 ratio in patients with severe pneumonia[J]. The Journal of Practical Medicine, 2024, 40(4): 515-520.

Figures/Tables 6

Tab.1

Tab.3

Tab. 4

Tab.5

Tab. 6

Fig. 1

References 22

1	ZENG S Z， XIE L Y， YU T， et al. Persistent viral shedding of human adenovirus type 7 in children with severe pneumonia［J］. J Med Virol， 2021，93（8）：4846-4855. doi:10.1002/jmv.26864 doi: 10.1002/jmv.26864
2	PUNSMANN S， HOPPE J， KLOPFLEISCH R， et al. Acute interstitial pneumonia in foals： A severe， multifactorial syndrome with lung tissue recovery in surviving foals［J］. Equine Vet J，2021，53（4）：718-726. doi:10.1111/evj.13355 doi: 10.1111/evj.13355
3	LONG M E， MALLAMPALLI R K， HOROWITZ J C. Pathogenesis of pneumonia and acute lung injury［J］. Clin Sci （Lond），2022，36（10）：747-769. doi:10.1042/cs20210879 doi: 10.1042/cs20210879
4	IONESCU M D， BALGRADEAN M， FILIP C， et al. The role of lung ultrasonography in predicting the clinical outcome of complicated community-acquired pneumonia in hospitalized children［J］. Med Ultrason， 2022，24（1）：19-26. doi:10.11152/mu-3124 doi: 10.11152/mu-3124
5	FATOBA A J， MAHARAJ L， ADELEKE V T， et al. Immunoinformatics prediction of overlapping CD8+ T-cell， IFN-γ and IL-4 inducer CD4+ T-cell and linear B-cell epitopes based vaccines against COVID-19 （SARS-CoV-2）［J］. Vaccine， 2021，39（7）：1111-1121. doi:10.1016/j.vaccine.2021.01.003 doi: 10.1016/j.vaccine.2021.01.003
6	ROJAS A， SCHNEIDER I， LINDNER C， et al. Receptor for advanced glycation end-products axis and coronavirus disease 2019 in inflammatory bowel diseases： A dangerous liaison？［J］. World J Gastroenterol， 2021，27（19）：2270-2280. doi:10.3748/wjg.v27.i19.2270 doi: 10.3748/wjg.v27.i19.2270
7	LEE H， LEE H H， LIM C Y， et al. The utility of high-mobility group A2 overexpression for predicting the prognosis of gastric cancer patients and its contribution to poor prognosis via chemoresistance and the propensity for the occurrence of carcinomatosis peritonei［J］. Surgery，2021，169（5）：1213-1220. doi:10.1016/j.surg.2020.11.020 doi: 10.1016/j.surg.2020.11.020
8	中华医学会儿科分会呼吸学组，《中华儿科杂志》编辑委员会，儿童社区获得性肺炎管理指南（2013修订）（上）［J］.中华儿科杂志，2013， 51（10）： 745-752.
9	中华医学会儿科分会呼吸学组，《中华儿科杂志》编辑委员会，儿童社区获得性肺炎管理指南（2013修订）（下）［J］.中华儿科杂志，2013， 51（11）： 856-862.
10	中华医学会重症医学分会. 急性肺损伤/急性呼吸窘迫综合征诊断和治疗指南（2006）［J］. 中国实用外科杂志， 2007，28（1）：19-28. doi:10.3321/j.issn:1005-2208.2007.01.001 doi: 10.3321/j.issn:1005-2208.2007.01.001
11	JUNG H Y， JEON Y， JEON S， et al. Superiority of Simplified Acute Physiologic Score II Compared with Acute Physiologic and Chronic Health Evaluation II and Sequential Organ Failure Assessment Scores for Predicting 48-Hour Mortality in Patients Receiving Continuous Kidney Replacement Therapy［J］. Nephron， 2022，146（4）：369-376. doi:10.1159/000521495 doi: 10.1159/000521495
12	BODIEN Y G， BARRA A， TEMKIN N R， et al. Diagnosing Level of Consciousness： The Limits of the Glasgow Coma Scale Total Score［J］. J Neurotrauma， 2021，38（23）：3295-3305.
13	SAGUIL A， FARGO M V. Acute Respiratory Distress Syndrome： Diagnosis and Management［J］. Am Fam Physician， 2020，101（12）：730-738.
14	ALHUMAID S， MUTARED K M AL， ALAWI Z AL， et al. Severity of SARS-CoV-2 infection in children with inborn errors of immunity （primary immunodeficiencies）： a systematic review［J］. Allergy Asthma Clin Immunol， 2023，19（1）：69. doi:10.1186/s13223-023-00831-1 doi: 10.1186/s13223-023-00831-1
15	LUYT C E， BOUADMA L， MORRIS A C， et al. Pulmonary infections complicating ARDS［J］. Intensive Care Med， 2020，46（12）：2168-2183. doi:10.1007/s00134-020-06292-z doi: 10.1007/s00134-020-06292-z
16	XU B， LIU X， GAO S. IL2-inducible T-cell kinase inhibitor ibrutinib reduces symptoms and Th2 differentiation in mouse allergic-rhinitis model［J］. Drug Dev Res， 2022，83（2）：544-551. doi:10.1002/ddr.21884 doi: 10.1002/ddr.21884
17	BLA VERÇOSA， MUNIZ-JUNQUEIRA M I， MENEZES-SOUZA D， et al. MCP-1/IL-12 ratio expressions correlated with adventitial collagen depositions in renal vessels and IL-4/IFN-γ expression correlated with interstitial collagen depositions in the kidneys of dogs with canine leishmaniasis［J］. Mol Immunol， 2023，156（3）：61-76. doi:10.1016/j.molimm.2023.02.010 doi: 10.1016/j.molimm.2023.02.010
18	KOTSIOU O S， JAGIRDAR R M， PAPAZOGLOU E D， et al. HΜGB1/sRAGE levels differ significantly between transudates and exudates［J］. Cytokine， 2021，141（4）：155469. doi:10.1016/j.cyto.2021.155469 doi: 10.1016/j.cyto.2021.155469
19	程茹，张素霞. 基于高迁移率族蛋白1/外泌体转录活化因子3途径探讨抗结核药吡嗪酰胺肝损伤的机制［J］. 实用医学杂志， 2023，39（10）：1224-1231. doi:10.3969/j.issn.1006-5725.2023.10.006 doi: 10.3969/j.issn.1006-5725.2023.10.006
20	郑强，唐勇，周程继，等. 乳果糖对失血性休克大鼠急性肺损伤的作用及机制［J］. 实用医学杂志， 2022，38（5）：577-582. doi:10.3969/j.issn.1006⁃5725.2022.05.011 doi: 10.3969/j.issn.1006?5725.2022.05.011
21	ENTEZARI M， JAVDAN M， ANTOINE D J， et al. Inhibition of extracellular HMGB1 attenuates hyperoxia-induced inflammatory acute lung injury［J］. Redox Biol， 2014，20（2）：314-322.
22	ZHAO H， CHEN H， XIAOYIN M， et al. Autophagy Activation Improves Lung Injury and Inflammation in Sepsis［J］. Inflammation， 2019，42（2）：426-439. doi:10.1007/s10753-018-00952-5 doi: 10.1007/s10753-018-00952-5

指标	ARDS组（n = 56）	对照组（n = 44）	t/χ ² 值	P值
性别［例（%）］			0.154 6	0.694 2
男	34（60.71）	25（56.82）
女	22（39.29）	19（43.18）
年龄（岁）	4.12 ± 1.03	4.26 ± 1.11	0.652 0	0.515 9
体温（℃）	37.87 ± 0.83	38.05 ± 0.97	0.999 3	0.320 1
发病季节［例（%）］			0.154 6	0.484 9
春夏	44（78.57）	37（84.09）
秋冬	12（21.43）	7（15.91）
致病菌种类［例（%）］			8.300 1	0.004 0
< 2种	17（30.36）	26（59.09）
≥ 2种	39（69.64）	18（40.91）
PaO₂ /FiO₂	175.68 ± 19.48	279.25 ± 26.28	22.632 3	0.000 0
APS（分）	28.89 ± 3.56	19.36 ± 4.12	12.397 2	0.000 0
机械通气OI	28.12 ± 3.26	-	-	-

组别	IFN-γ（μg/L）	IL-4（ng/L）	IFN-γ/IL-4
ARDS组（n = 56）	64.76 ± 8.69	99.96 ± 13.15	0.65 ± 0.09
对照组（n = 44）	53.20 ± 7.31	87.28 ± 12.87	0.61 ± 0.07
t值	7.072 5	4.831 3	2.426 5
P值	0.000 0	0.000 0	0.017 1

指标	回归系数	S.E.值	Wald	OR	P值	95%CI
常数	-14.184	1.542	84.611	-	< 0.001	-
致病菌种类	0.791	0.215	13.593	2.206	< 0.001	1.438 ~ 3.335
PaO₂/FiO₂	1.000	0.253	15.574	2.717	< 0.001	1.707 ~ 4.607
RAGE	0.659	0.199	10.944	1.932	0.001	1.229 ~ 2.682
HMGB1	0.866	0.210	17.035	2.378	< 0.001	1.514 ~ 3.447
IFN-γ	0.565	0.208	7.374	1.759	0.007	1.078 ~ 2.436
IL-4	0.698	0.194	12.937	2.010	< 0.001	1.320 ~ 2.825
IFN-γ/IL-4	0.876	0.257	11.607	2.402	0.001	1.227 ~ 3.363

相关指标	IFN-γ		IL-4		IFN-γ/IL-4
相关指标	r值	P值	r值	P值	r值	P值
RAGE	0.427	< 0.001	0.492	< 0.001	0.370	< 0.001
HMGB1	0.465	< 0.001	0.507	< 0.001	0.394	< 0.001

[1]	Bo YANG,Zhaoquan. JIN. The clinical efficacy of sivelestat sodium combined with ulinastatin for sepsis⁃induced acute respiratory distress syndrome [J]. The Journal of Practical Medicine, 2024, 40(5): 621-626.
[2]	Aiqin LI,Zhen ZHANG,Ya′nan XU,Jinyuan ZHU,Xu. ZHANG. Research progress on the interaction between macro⁃phages and fibroblasts in ARDS pulmonary fibrosis [J]. The Journal of Practical Medicine, 2024, 40(4): 571-574.
[3]	Feng ZHOU,Qixiang YIN,Faxing WEI,Haimin LIN,Huazhong CAI,Yikun. CHEN. The value of serum AQP1 level combined with EVLWI in assessing the severity and prognosis of ARDS due to sepsis [J]. The Journal of Practical Medicine, 2024, 40(17): 2483-2488.
[4]	Lichuang HUANG,Liangyan JIANG,Bixia ZHANG,Shaolei WU,Juntao HU,Zhanhong TANG. Interferon-γ Correlation with the severity of septic shock in patients and its prognostic value [J]. The Journal of Practical Medicine, 2024, 40(12): 1725-1730.
[5]	HE Dehua, LIU Ming, CHEN Qimin, LIU Xu.. Application of metagenomic next⁃generation sequencing in the etiological detection in patients with severe pneumonia [J]. The Journal of Practical Medicine, 2023, 39(8): 948-952.
[6]	HOU Yongzhe, ZHANG Qin, ZHAO Xiaochen, HE Miao, YU Lingling, BAI Hai, WU Tao.. Research progress of extracellular vesicles derived from mesenchymal stem cells in treatment of acute lung injury [J]. The Journal of Practical Medicine, 2023, 39(3): 390-394.
[7]	Xingle YANG,Tingting XIA,Chunlei ZUO,Jiaxin. SHI. Value of microbiology rapid on⁃site evaluation in severe pneumonia [J]. The Journal of Practical Medicine, 2023, 39(22): 2964-2968.
[8]	Ying LIU,Xianjun CHEN,Chuan XIAO,Jia YUAN,Qing LI,Lu LI,Jinfeng YANG,Feng. SHEN. Regulatory effect of LPAR1 gene on tissue factor and plasminogen activator inhibitor-1 in LPSstimulated type II alveolar epithelial cells [J]. The Journal of Practical Medicine, 2023, 39(18): 2323-2329.
[9]	Fei WEI,Xiangyu WANG,Zhiyong LIU. Effect of Xuebijing on lung tissue damage induced by Klebsiella pneumoniae in rats with severe pneumonia through miR⁃155/JAK2/STAT1 signaling pathway [J]. The Journal of Practical Medicine, 2023, 39(18): 2335-2341.
[10]	JIANG Jiali, CHEN Ting, TONG Wenjia, DING Jie, XU Weihua. . Expression and clinical significance of PI3K and MMP⁃9 in bronchoscopic alveolar lavage fluid of children with severe pneumonia in PICU [J]. The Journal of Practical Medicine, 2023, 39(15): 1939-1944.
[11]	WU Daorong, YAN Xuebo, WEN Tingyu, SONG Qiuming. . The evaluation value of serum and lower respiratory tract secretion SLPI in severe pneumonia in ICU [J]. The Journal of Practical Medicine, 2023, 39(12): 1529-1535.
[12]	LI Qing, GU Jiarun, XIAO Chuan, SHEN Feng, LIU Ying, LI Lu, HE Juan, LI Wei, LI Shuwen, LIU Bo, CHEN Xianjun.. Effects of gingerol on alveolar hypercoagulation and fibrinolytic inhibition in rats with LPS⁃induced acute respiratory distress syndrome [J]. The Journal of Practical Medicine, 2023, 39(10): 1218-1223.
[13]	ZHENG Xinghao , LI Qing, SHEN Feng, YANG Guixia, LI Xiang, XIAO Chuan.. Regulation of emodin on expressions of procoagulant and fibrinolytic inhibitors in LPS⁃stimulated alveolar epithelial cell type Ⅱ [J]. The Journal of Practical Medicine, 2022, 38(24): 3032-3036.
[14]	LI Jinlan, ZHANG Lizhong, FAN Liuru, LI Xiaoyan.. The role of Angiotensin⁃2 and soluble receptor for advanced glycation end products in the pathogenesis of septic associated Acute respiratory distress syndrome [J]. The Journal of Practical Medicine, 2022, 38(24): 3095-3105.
[15]	ZHANG Chunling, YANG Yuanjian, LIU Chang, ZHANG Weihua.. Clinical significance of serum PCT，BBP，IL⁃6 combined SOFA score in prognosis assessment of patients with severe pneumonia [J]. The Journal of Practical Medicine, 2022, 38(2): 168-172.

Correlation of serum RAGE and HMGB1 expression with the occurrence of acute respiratory distress syndrome and IFN⁃γ/IL⁃4 ratio in patients with severe pneumonia

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 6

References 22

Related Articles 15

Recommended Articles

Metrics

Comments