血清可溶性生长刺激表达基因2蛋白在预测急性胰腺炎严重程度及预后中的临床意义

贯芳; 丁锦; 王宇彤

doi:10.13201/j.issn.1009-5918.2022.09.004

血清可溶性生长刺激表达基因2蛋白在预测急性胰腺炎严重程度及预后中的临床意义

- 1.
  首都医科大学附属北京世纪坛医院消化内科(北京，100038)
- 2.
  首都医科大学附属北京世纪坛医院急诊科
基金项目:
北京市海淀区卫生健康发展科研培育计划(No：204106012)

详细信息

通讯作者: 贯芳，E-mail：guanfang@bjsjth.cn

中图分类号: R576

收稿日期: 2022-03-24

刊出日期: 2022-09-10

Clinical value of serum inflammatory marker ST2 in predicting the severity and prognosis of acute pancreatitis

- 1.
  Department of Gastroenterology, Beijing Shijitan Hospital Affiliated to Capital Medical University Haidian, Beijing, 100038, China
- 2.
  Department of Emergency, Beijing Shijitan Hospital Affiliated to Capital Medical University

More Information

Corresponding author: GUAN Fang, E-mail: guanfang@bjsjth.cn

Received Date: 24 March 2022

Publish Date: 10 September 2022

摘要

摘要: 目的探讨血清炎症标志物可溶性生长刺激表达基因2蛋白(sST2)与急性胰腺炎(AP)严重程度及预后的关系。方法选取2018年1月—2020年11月在首都医科大学附属北京世纪坛医院诊治的203例AP患者(AP组)，根据改良的Marshall评分进行器官功能衰竭评估，按AP严重程度分为轻度AP(MAP组)、中度AP(MSAP组)和重度AP(SAP组)。另选取100例我院健康体检者作为对照组。采用酶联免疫吸附法检测入院时、入院48 h后和缓解期(出院前24 h)血清sST2水平。结果与对照组相比，AP患者血清干扰素(IFN-γ)、白细胞介素-2(IL-2)、IL-4、IL-13、IL-33、sST2水平均升高，差异有统计学意义(P< 0.05)。然而只有血清sST2水平与疾病严重程度呈正相关(P< 0.05)。入院时血清sST2水平预测SAP的受试者工作特征曲线下面积为0.940(95%CI: 0.904~0.976)。血清sST2水平和急性生理与慢性健康评分Ⅱ(APACHE Ⅱ)、全身炎症反应综合征评分呈正相关(P< 0.001)。经单因素和多因素logistic回归分析，入院时血清sST2>526.0 pg/mL是预测患者院内死亡的独立危险因素(P< 0.05)。对于幸存的AP患者，与入院时相比，入院48 h、缓解期时血清sST2水平逐渐降低(P< 0.001)。结论血清sST2有可能成为AP诊断和监测疾病严重程度的候选生物标志物，同时也是患者院内死亡的独立预测因子。
- 急性胰腺炎 /
- 可溶性生长刺激表达基因2蛋白 /
- 严重程度 /
- 预后
Abstract: Objective To investigate the relationship between serum inflammatory marker soluble growth stimulation expression gene 2 protein(sST2) and severity and prognosis of acute pancreatitis(AP).Methods A total of 203 patients with AP treated in our hospital from January 2018 to November 2020 were selected. According to the improved Marshall score, they were divided into mild AP(MAP) group, moderate AP(MSAP) group and severe AP(SAP) group. A healthy control group of 100 patients were selected from local hospital staff. Serum sST2 levels were detected by enzyme-linked immunosorbent assay at admission, 48 hours after admission and in remission(24 hours before discharge).Results Compared with healthy control group, serum levels of interferon-γ, interleukin-2(IL-2), IL-4, IL-13, IL-33 and sST2 were increased in AP patients(P< 0.05). However, only serum sST2 levels were positively correlated with disease severity(P< 0.05). The area under the receiver operating characteristic curve for predicting SAP by serum sST2 level at admission was 0.940(95%CI: 0.904-0.976). There was positive correlation between serum sST2 level and acute physiology and chronic health score Ⅱ, systemic inflammatory response syndrome score(P< 0.001). Univariate and multivariate logistic regression analysis showed that admission serum ST2>526.0 pg/mL was an independent risk factor for predicting in-hospital death(P< 0.05). For the surviving AP patients, the level of serum sST2 decreased gradually at 48 hours of admission and remission compared with that at admission(P< 0.001).Conclusion sST2 may be a candidate biomarker for AP diagnosis and monitoring of disease severity, and it is also an independent predictor of in-hospital death.
- acute pancreatitis /
- soluble growth stimulation expressed gene 2 protein /
- severity /
- prognosis

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图 1 入院时血清sST2水平预测SAP进展的ROC曲线

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图 2 入院时血清sST2水平与疾病严重程度的关系(a)与APACHE Ⅱ评分和SIRS评分呈正相关(b)

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表 1 AP组和对照组血清炎症因子水平比较 pg/mL，M(P₂₅，P₇₅)

血清炎症因子	对照组(100例)	AP组(203例)	Z	P
IFN-γ	0.75(0.27，1.41)	1.50(0.90，2.20)	-2.895	0.017
IL-2	0.71(0.46，1.39)	1.07(0.70，1.68)	-2.491	0.038
IL-4	0.42(0.23，1.24)	0.99(0.43，2.42)	-3.158	0.005
IL-13	0.30(0.09，0.75)	0.87(0.69，1.18)	-3.251	0.001
IL-33	1.85(0.67，4.33)	7.34(5.71，9.85)	-5.179	< 0.001
sST2	117.85(68.91，189.65)	526.0(374.45，700.85)	-8.923	< 0.001

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表 2 AP患者一般资料及临床病理特征比较例(%)，M(P₂₅，P₇₅)

特征	MAP组(117例)	MSAP组(62例)	SAP组(24例)	χ²/F	P
年龄/岁	77.00(66.25，85.25)	73.00(52.75，81.25)	64.00(46.00，78.00)	0.790	0.674
男性	70(59.8)	39(62.9)	14(58.3)	0.219	0.897
BMI	22.68±4.30	22.76±3.89	23.83±4.15	0.777	0.461
病因学				10.227	0.596
胆结石	48(41.0)	20(32.2)	7(29.1)
过度饮酒	22(18.8)	16(25.8)	7(29.1)
特发性	36(30.7)	21(33.8)	8(33.3)
药源性	1(0.8)	1(1.6)	1(4.1)
胰肠吻合口狭窄	6(5.1)	0	1(4.1)
癌症	1(0.8)	2(3.2)	0
其他	3(2.5)	2(3.2)	0
肝硬化	2(1.71)	23(37.1)¹⁾	12(50.0)¹⁾	52.481	< 0.001
急性胰周积液	62(52.9)	31(50.0)	9(37.5)	1.914	0.384
炎症扩展至直肠膀胱	13(11.1)	9(14.5)	0	3.794	0.150
发病至入院时间/h	11.50(4.38，21.88)	15.75(5.63，25.88)	7.75(2.63，22.50)	1.580	0.454
Charlson合并症指数/分	0.50(0.00，2.00)	1.00(0.00，2.00)	0.00(0.00，0.75)	3.225	0.199
APACHE Ⅱ/分	9.00(6.25，10.00)	9.00(6.25，13.75)	12.00(8.25，16.50)¹⁾²⁾	22.585	< 0.001
SIRS评分/分	1.00(0.00，1.00)	1.00(0.00，2.00)	2.50(2.00，3.00)¹⁾²⁾	36.319	< 0.001
体温峰值/℃	36.81±0.83	36.97±0.84	36.77±0.78	0.898	0.409
脉搏/(次·min^-1)	85.00(77.25，98.50)	77.00(67.25，94.75)	71.50(61.00，89.00)	4.396	0.111
收缩压/mmHg	134.59±28.06	135.66±27.44	133.79±26.82	0.049	0.952
白细胞计数/(×10⁴·μL^-1)	11139.32±4855.80	11524.19±4052.67	10737.50±4915.88	0.281	0.755
血小板计数/(×10⁴·μL^-1)	21.72±7.64	21.41±4.22	22.80±6.97	0.376	0.687
CRP峰值/(mg·dL^-1)	0.54(0.22，3.02)	0.98(0.07，4.61)	0.68(0.18，2.20)	0.094	0.954
淀粉酶峰值/(U·L^-1)	1296.00(603.50，1563.75)	1764.50(748.50，3129.25)	1026.50(260.50，2527.75)	0.056	0.972
乳酸脱氢酶峰值/(U·L^-1)	314.50(244.75，395.00)	305.00(224.75，447.00)	258.00(220.75，420.25)	0.721	0.697
尿素氮峰值/(mg·dL^-1)	16.35(12.13，24.18)	19.60(13.93，34.05)	14.75(10.85，19.20)	2.515	0.284
血肌酐峰值/(mg·dL^-1)	0.75(0.55，0.83)	0.88(0.68，1.91)	0.72(0.65，0.87)	1.112	0.573
血钙峰值/(mg·dL^-1)	9.23±0.62	9.02±0.51	9.13±0.32	2.741	0.067
白蛋白峰值/(g·L^-1)	37.94±5.45	37.92±5.34	41.40±4.32¹⁾²⁾	12.835	< 0.001
总胆红素峰值/(μmol·L^-1)	1.10(0.83，2.03)	1.85(0.88，2.58)	1.70(1.13，2.38)	2.981	0.225
血清炎症因子
IFN-γ/(pg·mL^-1)	1.10(0.83，1.78)	1.70(1.13，2.50)	1.75(1.20，2.38)	2.463	0.292
IL-2/(pg·mL^-1)	1.03(0.53，1.63)	1.14(0.69，1.57)	1.27(0.74，2.23)	2.230	0.328
IL-4/(pg·mL^-1)	0.82(0.71，0.97)	0.83(0.63，1.35)	0.85(0.16，3.93)	0.786	0.675
IL-13/(pg·mL^-1)	0.80(0.59，1.15)	0.76(0.58，1.10)	0.86(0.71，1.19)	0.186	0.911
IL-33/(pg·mL^-1)	6.71(5.60，7.88)	7.78(6.06，10.03)	9.72(6.97，11.72)	5.654	0.059
sST2/(pg·mL^-1)	492.45(360.68，602.13)	589.85(458.90，748.08)	987.20(761.50，1355.25)	58.855	< 0.001
注：1 mmHg=0.133 kPa。与MAP组相比，¹⁾P < 0.05; 与MSAP组相比，²⁾P < 0.05。

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表 3 单因素和多因素logistic回归分析入院血清sST2与院内死亡的关系

血清sST2/(pg·mL^-1)	模型1		模型2		模型3
血清sST2/(pg·mL^-1)	HR(95%CI)	P	HR(95%CI)	P	HR(95%CI)	P
< 374.45	1.000	-	1.000	-	1.000	-
374.45~526.0	1.514(1.032~3.997)	0.019	1.019(1.001~3.457)	0.033	0.917(0.572~3.450)	0.413
>526.0~700.85	3.126(1.986~9.286)	< 0.001	1.971(1.224~6.850)	0.001	1.422(1.079~3.564)	0.007
>700.85	9.009(4.005~21.014)	< 0.001	4.375(2.019~11.423)	< 0.001	4.120(1.753~10.662)	< 0.001
注：模型1：单因素分析; 模型2：校正年龄、性别、BMI、Charlson合并症指数、发病至入院时间; 模型3：在模型2的基础上进一步校正体温、SBP、WBC、PLT以及其他实验室指标。

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