炎症细胞因子在脑脊液中的表达及与自发性脑出血严重程度和预后的相关性

doi:10.3969/j.issn.1006-5725.2025.22.013

Abstract

Abstract:

Objective To examine the expression levels of inflammatory factors， including IL-6， IL-10， MMP-9， IL-17A， and LDH， in the cerebrospinal fluid （CSF） of patients with spontaneous intracerebral hemorrhage （sICH）， and to investigate their associations with disease severity and clinical outcomes. Methods A total of 168 patients with sICH admitted to Tangshan GongRen Hospital between January 2023 and January 2025 were prospectively enrolled as the study group， while 30 non-sICH patients who underwent lumbar puncture during the same period served as the control group. Levels of inflammatory factors in CSF were compared between the two groups. Spearman′s rank correlation analysis was performed to assess the association between inflammatory factor levels and clinical severity in sICH patients. Binary logistic regression analysis was conducted to identify independent predictors of sICH prognosis. Receiver operating characteristic （ROC） curve analysis was employed to evaluate the prognostic value of these inflammatory factors in sICH. Results The levels of IL-6， IL-10， MMP-9， IL-17A， and LDH in the CSF of patients with sICH were significantly higher than those in non-sICH patients （all P < 0.05）. Furthermore， among sICH patients， these biomarker levels exhibited a graded increase according to disease severity： severe > moderate > mild （all P < 0.05）. Spearman correlation analysis revealed significant positive correlations between CSF levels of IL-6， IL-10， MMP-9， IL-17A， and LDH and the NIHSS scores， with correlation coefficients （r） of 0.686， 0.553， 0.685， 0.593， and 0.695， respectively （all P < 0.05）. When comparing the prognoses of sICH patients， hematoma size， NIHSS score， and CSF levels of IL-6， IL-10， MMP-9， IL-17A， and LDH were significantly higher in the deceased group than in the survival group （P < 0.05）， whereas ApoA1 levels were lower in the deceased group （P < 0.05）. Logistic regression analysis revealed that hematoma size， NIHSS score， and elevated CSF levels of IL-6， IL-10， MMP-9， IL-17A， and LDH were independent risk factors for mortality in sICH patients （P < 0.05）. ROC curve analysis showed that the AUC values for CSF IL-6， IL-10， MMP-9， IL-17A， and LDH in predicting sICH prognosis were 0.794， 0.754， 0.670， 0.717， and 0.683， respectively. Notably， the combination of CSF inflammatory markers with hematoma size and NIHSS score yielded an AUC of 0.993， demonstrating significantly greater predictive accuracy than CSF inflammatory markers alone （P < 0.05）. Conclusions The levels of inflammatory factors in the CSF， including IL-6， IL-10， MMP-9， IL-17A， and LDH， were elevated in patients with sICH and positively correlated with disease severity. Combining CSF inflammatory markers with the NIHSS score and hematoma size improved the predictive accuracy for sICH prognosis.

Key words: spontaneous intracerebral hemorrhage, cerebrospinal fluid, inflammation, condition, prognosis

CLC Number:

R743

Jianqiang WEI,Jing YIN,Mingyan HONG,Jianzhong CUI,Kaijie WANG,Hongyu WANG,Xinwang CAI,Wenqian ZHANG,Huan LIU. Study on the correlation between the expression of inflammatory cytokines in cerebrospinal fluid and the severity and prognosis of spontaneous intracerebral hemorrhage[J]. The Journal of Practical Medicine, 2025, 41(22): 3558-3565.

Figures/Tables 9

Tab.1

Comparison of general information of different"

指标	观察组（n = 168）	对照组（n = 30）	χ²/t值	P值
性别			0.635	0.426
男	108（64.29）	17（56.67）
女	60（35.71）	13（43.33）
年龄（ $x ˉ$ ± s）/岁	64.95 ± 10.49	64.20 ± 10.21	0.363	0.717
BMI（ $x ˉ$ ± s）/（kg/m²）	24.13 ± 3.45	23.90 ± 2.77	0.351	0.726
吸烟史			0.759	0.384
是	76（45.24）	11（36.67）
否	92（54.76）	19（63.33）
饮酒史			0.233	0.630
是	58（34.52）	9（30.00）
否	110（65.48）	21（70.00）

Tab.1

Fig.1

Tab.2

Tab.3

Fig.2

Tab.4

Tab.5

Tab.6

Fig.3

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指标	观察组（n = 168）	对照组（n = 30）	t值	P值
IL-6/（pg/mL）	90.58 ± 36.45	18.75 ± 8.33	10.722	< 0.001
IL-10/（pg/mL）	25.68 ± 12.84	8.24 ± 3.65	7.369	< 0.001
MMP-9/（ng/mL）	184.39 ± 62.75	52.27 ± 18.98	11.418	< 0.001
IL-17A/（pg/mL）	42.08 ± 20.88	12.15 ± 5.76	7.785	< 0.001
LDH/（U/L）	279.73 ± 101.66	156.12 ± 42.18	6.549	< 0.001

指标	轻度组（n = 78）	中度组（n = 62）	重度组（n = 28）	F值	P值
NIHSS评分/分	8.08 ± 3.47	22.65 ± 3.82^#	36.89 ± 3.73^#*	715.026	< 0.001
IL-6/（pg/mL）	65.37 ± 18.22	98.70 ± 25.31^#	142.82 ± 31.74^#*	116.831	< 0.001
IL-10/（pg/mL）	18.39 ± 7.20	28.51 ± 10.79^#	39.72 ± 15.26^#*	48.250	< 0.001
MMP-9/（ng/mL）	143.21 ± 32.59	194.67 ± 41.73^#	276.38 ± 58.95^#*	110.013	< 0.001
IL-17A/（pg/mL）	28.90 ± 11.30	46.70 ± 16.28^#	68.58 ± 21.30^#*	74.462	< 0.001
LDH/（U/L）	213.48 ± 52.71	295.82 ± 68.37^#	428.67 ± 95.70^#*	108.275	< 0.001

项目	死亡组（n = 38）	生存组（n = 130）	χ²/t值	P值
性别/［例（%）］			0.366	0.545
男	26（68.42）	82（63.08）
女	12（31.58）	48（36.92）
年龄/岁	63.24 ± 10.55	65.45 ± 10.46	1.147	0.253
BMI/（kg/m²）	23.54 ± 3.71	24.31 ± 3.36	1.198	0.233
高血压/［例（%）］			3.017	0.082
是	35（92.11）	104（80.00）
否	3（7.89）	26（20.00）
糖尿病/［例（%）］			1.134	0.287
是	12（31.58）	30（23.08）
否	26（68.42）	100（76.92）
吸烟史/［例（%）］			0.449	0.503
是	19（50.00）	57（43.85）
否	19（50.00）	73（56.15）
饮酒史/［例（%）］			0.532	0.466
是	15（39.47）	43（33.08）
否	23（60.53）	87（66.92）
收缩压/（mmHg）	163.08 ± 25.00	162.02 ± 24.64	0.232	0.817
舒张压/（mmHg）	93.05 ± 15.15	92.35 ± 14.87	0.254	0.166
出血部位/%
基底核	18（47.37）	78（60.00）	1.916	0.166
脑叶	12（31.58）	32（24.61）	0.738	0.390
小脑	5（13.16）	15（11.54）	0.074	0.786
脑干	3（7.89）	5（3.85）	1.063	0.303
血肿大小/mL	42.79 ± 18.6	28.52 ± 12.45	5.508	< 0.001
FPG/（mmol/L）	7.18 ± 2.15	6.86 ± 1.86	0.885	0.377
HbA1c/%	6.77 ± 1.44	6.48 ± 1.14	1.307	0.193
INS/（mU/L）	12.6 ± 4.85	11.75 ± 4.23	1.056	0.293
TC/（mmol/L）	4.64 ± 1.17	4.49 ± 1.01	0.760	0.448
TG/（mmol/L）	1.79 ± 0.61	1.65 ± 0.54	1.378	0.170
HDL-C/（mmol/L）	1.29 ± 0.33	1.25 ± 0.38	0.627	0.532
LDL-C/（mmol/L）	2.73 ± 0.76	2.59 ± 0.68	1.084	0.280
ApoA1/（g/L）	1.25 ± 0.31	1.39 ± 0.31	2.519	0.013
ApoB/（g/L）	0.91 ± 0.18	0.84 ± 0.19	1.913	0.057
NIHSS评分	27.84 ± 11.61	15.45 ± 9.52	6.701	< 0.001
IL-6/（pg/mL）	122.38 ± 39.86	81.28 ± 29.66	6.919	< 0.001
IL-10/（pg/mL）	35.34 ± 14.04	22.85 ± 11.02	5.755	< 0.001
MMP-9/（ng/mL）	223.97 ± 87.76	172.83 ± 47.88	4.689	< 0.001
IL-17A/（pg/mL）	55.54 ± 23.72	38.15 ± 18.27	4.808	< 0.001
LDH/（U/L）	345.37 ± 142.33	260.55 ± 77.00	4.815	< 0.001

指标	B	SE	Wald	P值	OR	95%CI
血肿大小	0.769	0.247	9.685	0.002	2.158	1.330 ~ 3.504
IL-6	0.216	0.043	25.636	< 0.001	1.241	1.141 ~ 1.349
IL-10	0.158	0.077	4.272	0.039	1.172	1.008 ~ 1.361
MMP-9	0.092	0.033	7.727	0.005	1.096	1.027 ~ 1.169
IL-17A	0.088	0.023	14.45	< 0.001	1.092	1.044 ~ 1.143
LDH	0.098	0.03	10.313	0.001	1.103	1.039 ~ 1.171
NIHSS评分	0.988	0.289	11.671	0.001	2.686	1.524 ~ 4.733

指标	AUC	SE	P值	95%置信区间		最佳截断值	灵敏度	特异度	约登指数
指标	AUC	SE	P值	下限	上限	最佳截断值	灵敏度	特异度	约登指数
IL-6	0.794	0.039	< 0.001	0.717	0.871	70.435 pg/mL	0.974	0.623	0.597
IL-10	0.754	0.044	< 0.001	0.667	0.840	18.395 pg/mL	0.895	0.654	0.549
MMP-9	0.670	0.061	0.001	0.550	0.791	166.545 ng/mL	0.684	0.500	0.184
IL-17A	0.717	0.046	< 0.001	0.627	0.807	35.43 pg/mL	0.789	0.569	0.358
LDH	0.683	0.060	0.001	0.566	0.801	270.73 U/L	0.632	0.600	0.232
联合	0.993	0.006	< 0.001	0.982	1.000	0.199	0.947	0.977	0.924

Study on the correlation between the expression of inflammatory cytokines in cerebrospinal fluid and the severity and prognosis of spontaneous intracerebral hemorrhage

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