IL-35和C3与脓毒症患者病情严重程度及预后的关系

doi:10.3969/j.issn.1673-8640.2021.01.005

摘要/Abstract

摘要：

目的探讨补体C3和白细胞介素35（IL-35）在脓毒症病情判断及预后评估中的价值。方法选取脓毒症患者80例,其中脓毒症45例（脓毒症组）、严重脓毒症患者35例（严重脓毒症组）[单器官功能障碍12例（单器官功能障碍组）、多器官功能障碍综合征（MODS）16例（MODS组）、死亡7例（死亡组）],收集所有患者的临床资料,在患者转入重症监护病房24 h内检测血常规[白细胞（WBC）计数、血小板（PLT）计数]、IgG、IgA、IgM、C3、C4、凝血酶原时间（PT）、国际标准化比值（INR）、活化部分凝血活酶时间（APTT）、纤维蛋白原（Fib）、丙氨酸氨基转移酶（ALT）、总胆红素（TB）、肌酐（Cr）、肌酸激酶MB同工酶（CK-MB）和IL-35,同时进行急性生理与慢性健康状况（APACHEⅡ）评分,并根据APACHEⅡ评分结果分为≤25分组和>25分组。结果脓毒症组C3、IL-35水平与严重脓毒症组比较,差异均有统计学意义（P<0.05）。单器官功能障碍组、MODS组及死亡组C3、IL-35水平与脓毒症组比较,差异均有统计学意义（P=0.001、P<0.001）,且随病情严重程度的增加,C3呈降低趋势,IL-35呈升高趋势。C3与PLT计数、Fib呈正相关（r值分别为0.32、0.52,P<0.001）,与PT、INR、APTT、ALT、TB、Cr、CK-MB均呈负相关（r值分别为-0.34、-0.38、-0.33、-0.31、-0.27、-0.25、-0.26,P<0.001）。IL-35与PLT、Fib呈负相关（r值分别为-0.33、-0.59,P<0.001）,与PT、INR、APTT、ALT、TB、Cr、CK-MB均呈正相关（r值分别为0.41、0.32、0.25、0.42、0.34、0.29、0.26,P<0.001）。APACHEⅡ评分≤25分组C3、IL-35水平与APACHEⅡ评分>25分组比较,差异均有统计学意义（P<0.05、P<0.001）,C3与预后（死亡）呈负相关（r=-0.63,P<0.05）,IL-35与预后（死亡）呈正相关性（r=0.54,P<0.001）。结论 C3和IL-35与脓毒症患者的凝血功能障碍及器官损伤有关,或可用于脓毒症的病情判断及预后评估。

关键词: 白细胞介素35, 补体, 脓毒症

Abstract:

Objective To analyze the relationship between complement 3（C3）,interleukin 35（IL-35）and the severity and prognosis of sepsis. Methods A total of 80 patients with sepsis were enrolled in this study,including 45 cases of general sepsis（general sepsis group）and 35 cases of severe sepsis（severe sepsis group）. In the severe sepsis group,there were 12 cases of single organ dysfunction（single organ dysfunction subgroup）,16 cases of multiple organ dysfunction syndrome（MODS subgroup）and 7 cases of death（death subgroup）. Clinical data of all patients were collected. Blood routine test [white blood cell（WBC） count,platelet（PLT） count],IgG,IgA,IgM,C3,C4,prothrombin time（PT）,international standardized ratio（INR）,activated partial thromboplastin time（APTT）,fibrinogen（Fib）,alanine aminotransferase（ALT）,total bilirubin（TB）,creatinine（Cr）,creatine kinase isoenzyme MB（CK-MB） and IL-35 were determined within 24 h after patients were transferred to intensive care unit（ICU）. Meanwhie, patients were evaluated by the acute physiology and chronic health evaluation Ⅱ（APACHEⅡ）,and were divided into different groups（APACHEⅡscore≤25 and APACHEⅡ score>25） according to the APACHEⅡ score. Results There were significant differences in the C3 and IL-35 between general sepsis group and severe sepsis group（P<0.05）. There were also significant differences in the C3 and IL-35 between subgroups and general sepsis group（P=0.001,P<0.001）. With the progression of the disease,C3 decreased and IL-35 increased. C3 was positively correlated with PLT and Fib（r=0.32 and 0.52,P<0.001）,and negatively correlated with PT,INR,APTT,ALT,TB,Cr and CK-MB（r=-0.34,-0.38,-0.33,-0.31,-0.27,-0.25 and -0.26,P<0.001）. IL-35 was negatively correlated with PLT and Fib（r=-0.33 and -0.59,P<0.001）,and positively correlated with PT,INR,APTT,ALT,TB,Cr and CK-MB（r=0.41,0.32,0.25,0.42、0.34,0.29 and 0.26,P<0.001）. There were significant differences in the C3 and IL-35 levels between patients with APACHEⅡscore≤25 and those with APACHEⅡ score>25（P<0.05,P<0.001）. C3 was negatively correlated with prognosis（death）（r=-0.63,P<0.05）,and IL-35 was positively correlated with prognosis（death）（r=0.54,P<0.001）. Conclusion C3 and IL-35 are involved in the coagulation disorders and organ damage in sepsis patients. They may be used to evaluate the condition and prognosis of sepsis.

Key words: Interleukin 35, Complement, Sepsis

中图分类号:

R446.1

胡森安, 艾红红, 叶雪莲, 成江燕. IL-35和C3与脓毒症患者病情严重程度及预后的关系[J]. 检验医学, 2021, 36(1): 25-29.

HU Senan, AI Honghong, YE Xuelian, CHENG Jiangyan. Relationship between complement 3,interleukin 35 and the severity and prognosis of sepsis[J]. Laboratory Medicine, 2021, 36(1): 25-29.

图/表 3

参考文献 11

[1]	COOPERSMITH C M,WUNSCH H,FINK M P,et al.A comparison of critical care research funding and the financial burden of critical illness in the United States[J]. Crit Care Med,2012,40(4):1072-1079.
[2]	王勇强,王兵. 脓毒症的诊治[J]. 中华急诊医学杂志,2013,22(2):222-224.
[3]	EGWUAGU C E,YU C R,SUN L,et al. Interleukin 35:critical regulator of immunity and lymphocyte-mediated diseases[J]. Cytokine Growth Factor Rev,2015,26(5):587-593.
[4]	CHARCHAFLIEH J,RUSHBROOK J,WORAH S,et al. Activated complement factors as disease markers for sepsis[J]. Dis Markers,2015,2015:382463.
[5]	LUPU F,KESHARI R S,LAMBRIS J D,et al. Crosstalk between the coagulation and complement systems in sepsis[J]. Thromb Res,2014,133(Suppl 1):S28-S31.
[6]	中国医学会重症医学分会. 中国严重脓毒症/脓毒性休克治疗指南(2014)[J]. 全科医学临床与教育,2015,13(4):365-367.
[7]	姚咏明,盛志勇. 脓毒症研究若干重要科学问题的思考[J]. 中华危重病急救医学,2016,28(2):102-103.
[8]	童森,祝筱梅,吴瑶,等. 拮抗高迁移率族蛋白B1对烫伤小鼠白细胞介素-35表达及T淋巴细胞免疫功能的影响[J]. 中国中西医结合急救杂志,2016,23(1):11-15.
[9]	WIRTZ S,BILLMEIER U,MCHEDLIDZE T,et al. Interleukin-35 mediates mucosal immune responses that protect against T-cell-dependent colitis[J]. Gastroenterology,2011,141(5):1875-1886.
[10]	BAI J,QIU S L,ZHONG X N,et al.Erythromycin enhances CD4+Foxp3+regulatory T-cell responses in a rat model of smoke-induced lung inflammation[J]. Mediators lnflamm,2012,2012:410232.
[11]	ZIMMER J,HOBKIRK J,MOHAMED F,et al.On the functional overlap between complement and anti-microbial peptides[J]. Front Immunol,2015,5:689.

组别	例数	年龄/岁			性别				WBC计数/ （×10⁹/L）			PLT计数/ （×10⁹/L）			IgG/（g/L）
组别	例数	年龄/岁			男/例	女/例			WBC计数/ （×10⁹/L）			PLT计数/ （×10⁹/L）			IgG/（g/L）
脓毒症组	45	57.71±9.02			24	21			15.21±4.22			214.52±64.23			7.27±1.54
严重脓毒症组	35	59.59±9.65			19	16			12.62±3.21			164.28±58.20			6.75±1.36
统计值		0.902			0.651				3.020			3.614			1.576
P值		0.370			0.530				0.003			0.001			0.119
组别	IgA/（g/L）			IgM/（g/L）				C3/（g/L）		C4/（g/L）			PT/s		INR	APTT/s
脓毒症组	0.42±0.12			0.85±0.17				0.99±0.41		0.19±0.09			11.25±2.23		1.05±0.12	36.8±4.21
严重脓毒症组	0.41±0.13			0.78±0.16				0.65±0.38		0.16±0.06			14.52±2.58		1.21±0.13	42.2±4.22
统计值	0.357			1.874				3.798		2.039			6.074		5.704	5.685
P值	0.722			0.065				<0.001		0.045			<0.001		<0.001	<0.001
组别	Fib/（g/L）		ALT/（U/L）				TB/（μmol/L）				Cr/（μmol/L）			CK-MB/（U/L）		IL-35/（pg/mL）
脓毒症组	2.63±0.71		35.56±13.25				7.85±2.21				34.28±4.02			35.45±11.24		28.58±6.65
严重脓毒症组	1.91±0.67		54.63±15.85				11.24±3.52				38.47±5.69			51.16±13.58		39.52±7.24
统计值	4.611		5.859				5.267				3.857			5.660		7.021
P值	<0.001		<0.001				<0.001				<0.001			<0.001		<0.001

组别	例数	年龄/岁			性别				WBC计数/ （×10⁹/L）			PLT计数/ （×10⁹/L）			IgG/（g/L）
组别	例数	年龄/岁			男/例	女/例			WBC计数/ （×10⁹/L）			PLT计数/ （×10⁹/L）			IgG/（g/L）
脓毒症组	45	57.71±9.02			24	21			15.21±4.22			214.52±64.23			7.27±1.54
严重脓毒症组	35	59.59±9.65			19	16			12.62±3.21			164.28±58.20			6.75±1.36
统计值		0.902			0.651				3.020			3.614			1.576
P值		0.370			0.530				0.003			0.001			0.119
组别	IgA/（g/L）			IgM/（g/L）				C3/（g/L）		C4/（g/L）			PT/s		INR	APTT/s
脓毒症组	0.42±0.12			0.85±0.17				0.99±0.41		0.19±0.09			11.25±2.23		1.05±0.12	36.8±4.21
严重脓毒症组	0.41±0.13			0.78±0.16				0.65±0.38		0.16±0.06			14.52±2.58		1.21±0.13	42.2±4.22
统计值	0.357			1.874				3.798		2.039			6.074		5.704	5.685
P值	0.722			0.065				<0.001		0.045			<0.001		<0.001	<0.001
组别	Fib/（g/L）		ALT/（U/L）				TB/（μmol/L）				Cr/（μmol/L）			CK-MB/（U/L）		IL-35/（pg/mL）
脓毒症组	2.63±0.71		35.56±13.25				7.85±2.21				34.28±4.02			35.45±11.24		28.58±6.65
严重脓毒症组	1.91±0.67		54.63±15.85				11.24±3.52				38.47±5.69			51.16±13.58		39.52±7.24
统计值	4.611		5.859				5.267				3.857			5.660		7.021
P值	<0.001		<0.001				<0.001				<0.001			<0.001		<0.001

组别	例数	C3/（g/L）	IL-35/（pg/mL）
脓毒症组	45	0.99±0.21	28.58±6.65
单器官功能障碍组	12	0.76±0.16	33.51±5.78
MODS组	16	0.65±0.13	41.62±7.24
死亡组	7	0.63±0.12	52.44±7.86
F值		33.03	54.21
P值		0.001	<0.001

组别	例数	C3/（g/L）	IL-35/（pg/mL）
脓毒症组	45	0.99±0.21	28.58±6.65
单器官功能障碍组	12	0.76±0.16	33.51±5.78
MODS组	16	0.65±0.13	41.62±7.24
死亡组	7	0.63±0.12	52.44±7.86
F值		33.03	54.21
P值		0.001	<0.001

APACHEⅡ评分	例数	C3/（g/L）	IL-35/（pg/mL）
≤25分组	42	0.88±0.44	31.24±7.51
>25分组	38	0.65±0.42	42.54±8.42
t值		2.354	6.345
P值		<0.05	<0.001