切换至 "中华医学电子期刊资源库"

中华肺部疾病杂志(电子版) ›› 2024, Vol. 17 ›› Issue (06) : 869 -874. doi: 10.3877/cma.j.issn.1674-6902.2024.06.004

论著

结缔组织相关性间质性肺病血清S1P 水平与疾病严重程度和免疫抑制治疗的关系
韩晓1, 汤凤莲1, 张友文1, 吕高超1, 姜波1, 王利江1,()   
  1. 1.272000 济宁,济宁医学院附属医院呼吸与危重症医学科
  • 收稿日期:2024-07-17 出版日期:2024-12-25
  • 通信作者: 王利江
  • 基金资助:
    国家自然科学基金青年科学基金(82400034)2019 年度济宁医学院教师科研扶持基金(JYFC2019FKJ129)

Association of serum S1P with disease severity and immunosuppressive therapy in connective tissueassociated interstitial lung disease

Xiao Han1, Fenglian Tang1, Youwen Zhang1, Gaochao Lv1, Bo Jiang1, Lijiang Wang1,()   

  1. 1.Department of Respiratory and Critical Care Medicine, Jining Medical College Affiliated Hospital,Jining, Shandong 272000, China
  • Received:2024-07-17 Published:2024-12-25
  • Corresponding author: Lijiang Wang
引用本文:

韩晓, 汤凤莲, 张友文, 吕高超, 姜波, 王利江. 结缔组织相关性间质性肺病血清S1P 水平与疾病严重程度和免疫抑制治疗的关系[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(06): 869-874.

Xiao Han, Fenglian Tang, Youwen Zhang, Gaochao Lv, Bo Jiang, Lijiang Wang. Association of serum S1P with disease severity and immunosuppressive therapy in connective tissueassociated interstitial lung disease[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2024, 17(06): 869-874.

目的

分析结缔组织相关间质性肺病(connective tissue disease-associated interstitial lung disease,CTD-ILD)血清1-磷酸鞘氨醇(sphingosine 1-phosphate,S1P)水平与疾病严重程度和免疫抑制治疗的关系。

方法

选择2022 年12 月至2024 年1 月我院收治的85 例CTD-ILD 患者为对象。 利用一氧化碳弥散量占预计值百分比(carbon monoxide dispersion as a percentage of the expected value,DLCO%)和高分辨率CT(high resolution ct,HRCT)判断CTD-ILD 疾病严重程度和肺累及范围。 经标准环磷酰胺(cyclophosphamide,CTX)冲击治疗,通过酶联免疫吸附法检测CTD-ILD 血清S1P 水平。 采用Spearman法判断血清S1P 与肺功能的关系。

结果

85 例中轻度CTD-ILD 34 例(40.00%)、中度38 例(44.71%)和重度13 例(15.29%)。 中度和重度者较轻度者用力肺活量占预计值百分比(forced vital capacity%,FVC%)、1 秒用力呼气容积占预计值百分比(forced expiratory volume in one second,FEV1%)、DLCO%降低(P<0.05)。 轻度CTD-ILD 血清S1P 水平663.70(249.76,1 045.27)ng/ml、中度CTD-ILD 血清S1P 水平877.47(705.31,1 861.98)ng/ml 和重度CTD-ILD 血清S1P 水平1 624.38(1 016.52,3 753.87)ng/ml(P<0.001)。 Spearman 法和多元线性回归分析显示,CTD-ILD 血清S1P 水平与FVC%(β=-0.009,t=-3.943,P<0.001)、FEV1%(β=-0.009,t=-3.912,P<0.001)、DLCO%(β=-0.008,t=-3.871,P<0.001)呈负相关。 经CTX 冲击治疗后缓解64 例(75.29%),无效21 例(24.71%)。 缓解者PLT/LYM 比值129.06(88.64,184.32)和CRP 水平4.99(3.30,20.07)mg/L 低于无效者PLT/LYM 比值193.62(120.24,265.94)和CRP 水平11.90(3.69,31.07)mg/L(P<0.05)。 治疗后缓解者血清S1P 水平851.13(412.68,1 497.11)ng/ml 低于无效者血清S1P 水平962.07(438.99,1 561.03)ng/ml(P<0.05)。

结论

经CTX 冲击治疗缓解者血清S1P 水平降低,血清S1P 可识别CTD-ILD 疾病严重程度,具有临床意义。

Objective

To investigate the relationship between serum sphingosine 1-phosphate (S1P)level,disease severity and immunosuppressive therapy in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD).

Methods

All of 85 cases of CTD-ILD patients admitted to the Department of Respiratory and Critical Care Medicine,Affiliated Hospital of Jining Medical College from December 2022 to January 2024 were selected as the study objects.The severity of CTD-ILD disease and the extent of lung involvement were assessed using carbon monoxide dispersion as a percentage of expected value(DLCO%) and high-resolution CT ( HRCT) scanning.All CTD-ILD patients received standard cyclophosphamide (CTX) impulse therapy and were divided into response subgroup and response subgroup according to treatment effect.Serum S1P levels in CTD-ILD patients were detected by enzyme-linked immunosorbent assay at baseline,3 months after treatment and 6 months after treatment.Spearman method was used to evaluate the relationship between serum S1P and other indicators.

Results

In the 85 cases,34 cases(40.00%) were mild CTD-ILD,38 cases (44.71%) were moderate CTD-ILD,and 13 cases (15.29%) were severe CTD-ILD.Compared with mild patients,lung function (FVC%,FEV1%,DLCO%) was significantly decreased in moderate and severe patients (F=20.206, F=33.587, F=71.133, P<0.05).The baseline serum S1P levels of CTD-ILD patients in mild,moderate and severe groups were 663.70 (249.76,1 045.27) ng/ml,877.47 (705.31,1 861.98) ng/ml and 1 624.38 (1 016.52,3 753.87) ng/ml(H=14.028, P<0.001).Spearman and multivariate linear regression analysis showed that baseline serum S1P level in CTD-ILD patients was correlated with FVC% (β=-0.009, t=-3.943, P<0.001),FEV1% (β=-0.009, t=-3.912, P<0.001),DLCO% (nonstandardized coefficient β = -0.008, t = -3.871, P <0.001) was still negatively correlated.After CTX shock therapy,all 85 CDT-ILD patients received HRCT scans and PFT at three time points,64 patients were diagnosed as effective or stable (response subgroup),and the remaining 21 patients(24.71%) were classified as ineffective subgroup.The baseline PLT/LYM ratio[129.06(88.64,184.32)vs.193.62(120.24,265.94)] and CRP level[4.99(3.30,20.07)mg/L vs. 11.90(3.69,31.07)mg/L] in the remission subgroup were slightly lower than those in the ineffective subgroup (P<0.05).Further trend analysis showed that the serum S1P level in the remission subgroup gradually decreased over time,and at 3 and 6 months after treatment,the serum S1P level[851.13(412.68,1 497.11)ng/ml vs. 962.07(438.99,1 561.03)ng/ml] in the remission subgroup was lower than that in the ineffective subgroup (P<0.05).

Conclusion

Serum S1P levels tend to decrease in patients who are in remission after CTX shock therapy,S1P may also be a supportive indicator of treatment effectiveness in CTD-ILD patients.

表1 不同疾病严重程度CTD-ILD 患者临床资料比较[n(%),M(M25,M75)]
表2 血清S1P 水平与肺功能和炎症指标关系
表3 血清S1P、肺功能及实验室指标结果[M(M25,M75)]
1
Storrer KM,Müller CS,Pessoa MCA,et al.Connective tissue disease-associated interstitial lung disease [J].J Brasileiro de Pneumolog,2024,50(1):e20230132.
2
黄 慧.间质性肺疾病年度进展2023[J].中华结核和呼吸杂志,2024,47(1):44-49.
3
董学峰,常 乐,蔡振煜.血清ESR、CRP 及PLR、MLR 联合诊断结缔组织相关性间质性肺炎的意义[J/CD].中华肺部疾病杂志(电子版),2024,17(3):430-433.
4
梁 洁,陈玉兰,卢睿凌,等.结缔组织病相关间质性肺病血清生物标志物的研究进展[J].中华内科杂志,2024,63(3):310-315.
5
Bravo GÁ,Cedeño RR,Casadevall MP,et al.Sphingosine-1-phosphate(S1P) and S1P signaling pathway modulators,from current insights to future perspectives[J].Cells,2022,11(13):2058-2071.
6
蒋 艳,张韶泽,曾 丹,等.1-磷酸鞘氨醇在呼吸系统疾病中的研究进展[J].中国医师杂志,2021,23(12):1909-1913.
7
Hutami IR.The roles of sphingosine-1-phosphate (S1p) on arthritis[J].Odonto:Dental J,2024,11(1):115-123.
8
Li J,Huang Y,Zhang Y,et al.S1P/S1PR signaling pathway advancements in autoimmune diseases[J].Biomol Biomed,2023,23(6):922-935.
9
Tanaka T,Koyama K,Takahashi N,et al.Lysophosphatidic acid,ceramide 1-phosphate and sphingosine 1-phosphate in peripheral blood of patients with idiopathic pulmonary fibrosis[J].J Med Investigat,2022,69(3.4):196-203.
10
American Thoracic Society; European Respiratory Society.American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias.This joint statement of the American Thoracic Society (ATS),and the European Respiratory Society(ERS) was adopted by the ATS board of directors,June 2001 and by the ERS Executive Committee,June 2001 [J].Am J Respir Crit Care Med,2002,165(2):277-304.
11
孙英梅,闫慧明.血清MMP-7、ADAM17 在结缔组织病相关间质性肺病中的表达及相关性研究[J].风湿病与关节炎,2024,13(5):20-26.
12
Singh N,Dorfmüller P,Shlobin OA,et al.Group 3 pulmonary hypertension:from bench to bedside[J].Circ Res,2022,130(9):1404-1422.
13
Beghé B,Cerri S,Fabbri LM,et al.COPD,pulmonary fibrosis and ILAs in aging smokers:the paradox of striking different responses to the major risk factors[J].Int J Mol Sci,2021,22(17):9292.
14
Sweis JJG,Sweis NWG,Alnaimat F,et al.Immune-mediated lung diseases:A narrative review[J].Front Med (Lausanne),2023,10:1160755.
15
Atzeni F,Alciati A,Gozza F,et al.Interstitial lung disease in rheumatic diseases:an update of the 2018 review [J].Expert Rev Clin Immunol,2024:1-18.
16
Li J,Huang Y,Zhang Y,et al.S1P/S1PR signaling pathway advancements in autoimmune diseases[J].Biomol Biomed,2023,23(6):922.
17
Verstockt B,Vetrano S,Salas A,et al.Sphingosine 1-phosphate modulation and immune cell trafficking in inflammatory bowel disease[J].Nat Rev Gastroenterol Hepatol,2022,19(6):351-366.
18
Alqalyoobi S,Adegunsoye A,Linderholm A,et al.Circulating plasma biomarkers of progressive interstitial lung disease[J].Am J Respir Crit Care Med,2020,201:250-253.
19
Lewis KL,Helgeson SA,Tatari MM,et al.COVID-19 and the effects on pulmonary function following infection:a retrospective analysis[J].E Clin Med,2021,39:101079.
20
Huang LS,Berdyshev EV,Tran JT,et al.Sphingosine-1-phosphate lyase is an endogenous suppressor of pulmonary fibrosis:role of S1P signalling and autophagy[J].Thorax,2015,70:1138-1148.
21
王梦琰,崔 培,辛海明.1-磷酸鞘氨醇在急性肺损伤中的作用研究进展[J].中华烧伤与创面修复杂志,2022,38(5):496-500.
22
Donati C,Cencetti F,Bernacchioni C,et al.Role of sphingosine 1-phosphate signalling in tissue fibrosis[J].Cell Signal,2021,78:109861.
23
Fan X,Liu L,Shi Y,et al.Recent advances of the function of sphingosine 1-phosphate (S1P) receptor S1P3[J].J Cell Physiol,2021,236(3):1564-1578.
24
Terlizzi M,Colarusso C,Somma P,et al.S1P-Induced TNF-α and IL-6 release from PBMCs exacerbates lung cancer-associated inflammation[J].Cells,2022,11(16):2524-2535.
25
Qin HY,Li MD,Xie GF,et al.Associations among S100A4,sphingosine-1-phosphate,and pulmonary function in patients with chronic obstructive pulmonary disease [J].Oxidat Med Cellul Longevity,2022,2022(1):6041471-6041479.
26
Suryadevara V,Ramchandran R,Kamp DW,et al.Lipid mediators regulate pulmonary fibrosis:potential mechanisms and signaling pathways[J].Int J Mol Sci,2020,21(12):4257.
27
Jayant G,Kuperberg S,Somnay K,et al.The role of sphingolipids in regulating vascular permeability in idiopathic pulmonary fibrosis[J].Biomedicines,2023,11(6):1728-1742.
28
Huang LS,Sudhadevi T,Fu P,et al.Sphingosine Kinase 1/S1P signaling contributes to pulmonary fibrosis by activating Hippo/YAP Pathway and mitochondrial reactive oxygen species in lung fibroblasts[J].Int J Mol Sci,2020,21(6):2064-2085.
29
Cartier A,Hla T.Sphingosine 1-phosphate:Lipid signaling in pathology and therapy[J].Science,2019,366(6463):eaar5551.
30
Ouyang J,Shu Z,Chen S,et al.The role of sphingosine 1-phosphate and its receptors in cardiovascular diseases[J].J Cell Mol Med,2020,24(18):10290-10301.
[1] 罗霞, 王宝梅, 李淑景, 杨英. 特发性肺动脉高压血清PCSK9表达及预后意义[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(04): 585-589.
[2] 程炜炜, 张青, 张诚实, 冯契靓, 陈荣荣, 赵云峰. 全身免疫炎症指数与慢性阻塞性肺疾病急性加重期病情严重程度相关性分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(04): 580-584.
[3] 宋玮, 黄修丽, 李鑫, 史雅琼, 张晔, 邓飞, 高燕. 改良衰弱指数对重症肺部感染的预后分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(01): 119-122.
[4] 张黎黎, 杨敏, 石娅妮, 谭红霞. MR-proADM作为社区获得性肺炎预后生物标志物的临床分析[J/OL]. 中华肺部疾病杂志(电子版), 2023, 16(05): 706-708.
[5] 罗婷, 张实. 5种生物标志物对ARDS预后的预测分析[J/OL]. 中华肺部疾病杂志(电子版), 2023, 16(04): 471-475.
[6] 张沥, 宋俊华, 何皓, 杨雪瑶, 周康. 血清D-D、PAI-1、sICAM-1水平与糖尿病合并肺部感染病情严重程度及预后的关系[J/OL]. 中华肺部疾病杂志(电子版), 2023, 16(02): 203-205.
[7] 李琼, 张庭秀, 胡绳, 周宏. 支气管扩张患者TNF-α、IL-6、中性粒细胞百分比与疾病严重程度的关系[J/OL]. 中华肺部疾病杂志(电子版), 2022, 15(05): 649-652.
[8] 要丹丹, 陈会娟, 南雨杰. 2D-STE评价OSAS患者心功能指标与疾病严重程度的分析[J/OL]. 中华肺部疾病杂志(电子版), 2022, 15(03): 358-360.
[9] 胡欣芫, 杨智義, 赵成俊, 张秋雨, 张挽乾, 潘佰猛, 张灵强. 急性胰腺炎评分系统预测病情严重程度的研究进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(02): 239-243.
[10] 吴志杰, 袁紫旭, 蔡建, 柯嘉, 王辉. 腹膜转移癌诊疗决策中评分系统的研究进展[J/OL]. 中华结直肠疾病电子杂志, 2023, 12(01): 75-78.
[11] 王召, 田进杰, 郭朝, 王蕾, 严红燕, 冯素娟, 张毅. 血浆PGK1早期检测对创伤性颅脑损伤患者病情严重程度及预后的预测价值[J/OL]. 中华神经创伤外科电子杂志, 2023, 09(03): 154-159.
[12] 孙斌, 何宗钊, 王皓, 王婷, 刘晓琴. 西宁地区高血压脑出血手术患者严重程度与炎症反应变化特征的观察研究[J/OL]. 中华重症医学电子杂志, 2023, 09(01): 62-68.
[13] 吉茜茜, 田尧, 马林, 钱进. 红细胞分布宽度-白蛋白比值联合BISAP评分对急性胰腺炎严重程度及死亡率的预测价值[J/OL]. 中华消化病与影像杂志(电子版), 2023, 13(06): 433-438.
[14] 苏家光, 黄家灿, 潘延斌, 郑文军. 银屑病患者中趋化素与皮损、肥胖、糖脂代谢及炎症因子的相关性[J/OL]. 中华临床医师杂志(电子版), 2022, 16(06): 513-518.
[15] 胡奕卿, 黄钰晨, 罗璐, 方继伟, 刘焕兵. 肌少症评估对中老年急性胰腺炎患者的临床预测价值[J/OL]. 中华老年病研究电子杂志, 2022, 09(03): 1-5.
阅读次数
全文


摘要