急性脑梗死患者血清BDNF、IL-18、hs-CRP水平与血管性认知障碍的相关性

doi:10.19723/j.issn.1671-167X.2024.04.026

摘要/Abstract

摘要：

目的: 探讨急性脑梗死患者血清脑源性神经营养因子(brain-derived neurotrophic factor，BDNF)、白细胞介素18(interleukin-18，IL-18)、超敏C反应蛋白(hypersensitivity C-reactive protein，hs-CRP)水平与血管性认知障碍(vascular cognitive impairment，VCI)的相关性，为早期预防VCI提供有价值的临床依据。方法: 选取山西晋城市人民医院神经内科2019年5月至2020年4月急性脑梗死住院患者160例，按照是否合并认知障碍分为无认知障碍组(no cognitive impairment，NCI，57例)、非痴呆型血管性认知障碍组(vascular cognitive impairment no dementia，VCIND，56例)和血管性痴呆组(vascular dementia，VaD，47例)。采用蒙特利尔认知评估量表(Montreal cognitive assessment，MoCA)测评各组患者的认知功能，采用美国国立卫生研究院卒中量表(National Institute of Health stroke scale，NIHSS)评估患者的神经缺损程度(分为轻度组、中度组、重度组)，采用Pullicino梗死灶面积计算方法计算梗死面积(分为小面积梗死组、中面积梗死组、大面积梗死组)。分别在脑梗死急性期(0~7 d)、恢复期(15~30 d)和6个月时，采用酶联免疫吸附试验(enzyme-linked immunosorbent assay，ELISA)检测各组患者血清BDNF、IL-18的含量，采用免疫比浊法测定血清hs-CRP的水平。观察不同程度神经功能缺损和不同梗死面积对血清BDNF、IL-18、hs-CRP的影响，比较NCI、VCIND和VaD三组患者BDNF、IL-18和hs-CRP的表达水平，分析其与VCI的相关性。结果: (1) 神经功能缺损轻度组、小面积梗死组血清BDNF的水平和MoCA评分分别显著高于缺损中、重度组和中面积、大面积梗死组，其血清IL-18、hs-CRP水平分别显著低于缺损中、重度组和中面积、大面积梗死组，差异均有统计学意义(P＜0.05)；(2)NCI组、VCIND组、VaD组的BDNF水平在脑梗死急性期、恢复期和6个月时均呈递减趋势，急性期和恢复期差异有统计学意义(P＜0.05)，三组IL-18、hs-CRP水平在急性期、恢复期和6个月时均呈递增趋势，差异有统计学意义(P＜0.05)；(3)血清BDNF水平与MoCA评分呈正相关，与VCI的严重程度呈负相关，而IL-18、hs-CRP水平与MoCA评分呈负相关，与VCI的严重程度呈正相关。结论: 血清BDNF、IL-18和hs-CRP参与了急性脑梗死后VCI发生发展的病理过程，BDNF发挥了积极的保护作用，IL-18和hs-CRP对认知功能造成了明显的损害，血清BDNF、IL-18和hs-CRP的表达水平与认知障碍的严重程度密切相关，可以作为VCI早期诊断的生物标记物。

关键词: 脑梗死, 血管性认知障碍, 脑源性神经营养因子, 白细胞介素18, 超敏C反应蛋白

Abstract:

Objective: To explore the correlations between serum levels of brain-derived neurotrophic factor (BDNF), interleukin-18 (IL-18) and hypersensitivity C-reactive protein (hs-CRP) in patients with acute cerebral infarction and vascular cognitive impairment (VCI), and to provide some clinical bases for early prevention of VCI. Methods: A total of 160 patients with acute cerebral infarction admitted in Department of Neurology of Jincheng People' s Hospital from May 2019 to April 2020 were enrolled in this study and were devided into three groups according to whether or not combined with cognitive impairment, including no cognitive impairment group (NCI, 57 cases), vascular cognitive impairment no dementia group (VCIND, 56 cases) and vascular dementia group (VaD, 47 cases). The cognitive function of all the patients were evaluated by Montreal cognitive assessment (MoCA). The National Institute of Health stroke scale (NIHSS) was used to assess the degree of neurological deficit (mild-, moderate-, severe-neurologic deficit group). The infarct size was calculated by Pullicino' s method (small-, middle-, large-infarct group). The levels of serum BDNF and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA), and serum levels of hs-CRP were measured by immunoturbidimetry during the acute phase (0-7 d), recovery period (15-30 d) and 6 months after cerebral infarction. The effects of varying degrees of neurological deficits and different size of infarction on BDNF, IL-18 and hs-CRP were observed. The levels of serum BDNF, IL-18 and hs-CRP in the patients of the three groups with acute, convalescent and six-month cerebral infarction were compared, and their correlations with VCI were analyzed. Results: Serum BDNF level and MoCA scores in mild-neurologic deficit group and small-infarct group were significantly higher than those in moderate- and severe-deficit group, middle- and large-infarct group, respectively (P < 0.05). Their levels of IL-18 and hs-CRP were significantly lower than those in moderate- and severe-deficit group, middle- and large-infarct group, respectively (P < 0.05). The levels of serum BDNF in NCI group, VCIND group and VaD group during the acute phase, convalescence and 6 months after cerebral infarction were in a significant decline, and the differences during the acute phase and recovery period were statistically significant (P < 0.05). The levels of IL-18 and hs-CRP during the acute phase, recovery period and 6 months after cerebral infarction showed a significant increasing trend with significance (P < 0.05). Correlation analysis revealed that the levels of BDNF was positively correlated with MoCA scores but negatively correlated with the severity of cognitive impairment while the expression levels of IL-18 and hs-CRP were negatively correlated with MoCA scores but positively correlated with the severity of cognitive impairment. Conclusion: Serum BDNF, IL-18 and hs-CRP are involved in the pathological process of occurrence and development of VCI in the patients with acute cerebral infarction. BDNF has a protective effect on VCI while IL-18 and hs-CRP cause severe cognitive impairment. The levels of serum BDNF、IL-18 and hs-CRP in the patients with acute ischemic cerebral infarction are closely related to the severity of cognitive impairment and can be used as biomarkers of early diagnosis of VCI.

Key words: Brain infarction, Vascular cognitive impairment, Brain-derived neurotrophic factor, Interleukin-18, Hypersensitivity C-reactive protein

中图分类号:

R749.13

李晋娜,许丽娜,李敏,宋怡,张静,贾龙斌. 急性脑梗死患者血清BDNF、IL-18、hs-CRP水平与血管性认知障碍的相关性[J]. 北京大学学报（医学版）, 2024, 56(4): 708-714.

Jinna LI,Li' na XU,Min LI,Yi SONG,Jing ZHANG,Longbin JIA. Correlations between serum BDNF, IL-18 and hs-CRP levels in patients with acute cerebral infarction and vascular cognitive impairment[J]. Journal of Peking University (Health Sciences), 2024, 56(4): 708-714.

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Research indexes	NCI group (n=57)	VCIND group (n=56)	VaD group (n=47)	χ²/F	P
Gender (male), n (%)	35 (61.4)	32 (57.1)	28 (59.6)	0.214	0.899
Age/ years, $\bar x \pm s$	62.93±7.54	64.33±7.78	65.02±8.86	2.170	0.446
Years of education, $\bar x \pm s$	8.62±3.04	8.41±3.17	7.97±2.88	1.684	0.831
Smoking, n (%)	11 (19.3)	18 (32.1)	19 (40.4)	5.164	0.059
Drinking, n (%)	14 (24.6)	12 (21.4)	14 (29.8)	0.961	0.618
Hypertension, n (%)	16 (28.1)	19 (33.9)	19 (40.4)	1.402	0.496
Diabetes, n (%)	10 (17.5)	11 (19.6)	13 (27.7)	1.708	0.426
Hyperlipemia, n (%)	11 (19.3)	13 (23.2)	15 (31.9)	2.287	0.319
History of stroke, n (%)	12 (21.1)	16 (28.6)	17 (36.2)	2.230	0.328
NIHSS, M (P₂₅, P₇₅)	1 (1, 4)	1 (1, 4)	2 (1, 4)	2.228	0.033
Classification of cerebral infarction, n (%)
Partial anterior Circulation infarction	16 (28.07)	16 (28.57)	12 (25.53)	0.237	0.751
Subcortical infarction	29 (50.88)	27 (48.21)	23 (48.94)	0.316	0.584
Posterior circulation infarction	12 (21.05)	13 (23.21)	12 (25.53)	0.441	0.528
Infarct area, n (%)
Large infarct	0 (0)	8 (14.29)	20 (42.55)	7.153	0.014
Middle infarct	3 (8.77)	34 (60.71)	18 (38.30)	6.278	0.026
Small infarct	54 (94.74)	14 (25.00)	9 (19.15)	7.144	0.034

Items	Neurologic deficit group					Infarct area group
Items	Mild (n=82)	Moderate (n=52)	Severe (n=26)	F	P	Small (n=77)	Middle (n=55)	Large (n=28)	F	P
BDNF/(μg/L)	5.66±2.48^ab	4.89±2.33^a	3.71±2.62	14.152	0.031	5.78±1.61^cd	5.02±2.07^c	3.55±1.43	14.761	0.028
IL-18/(ng/L)	27.57±2.94^ab	43.57±3.45^a	64.57±4.83	15.184	0.024	23.57±1.94^cd	38.87±4.65^c	68.50±5.39	16.214	0.019
hs-CRP/(mg/L)	5.95±2.63^ab	11.73±4.04^a	24.32±6.76	18.393	0.013	5.67±1.48^cd	13.16±3.54^c	26.08±7.79	23.545	0.009
MoCA scores	24.57±1.94^ab	15.44±2.11^a	10.35±3.25	11.267	0.037	25.70±2.26^cd	16.73±2.48^c	9.89±3.16	13.376	0.033

Groups	n	Acute phase			Convalescence period			At 6 months
Groups	n	BDNF/(μg/L)	IL-18/(ng/L)	hs-CRP/(mg/L)	BDNF/(μg/L)	IL-18/(ng/L)	hs-CRP/(mg/L)	BDNF/(μg/L)	IL-18/(ng/L)	hs-CRP/(mg/L)
NCI group	57	5.74±2.52^a	27.92±4.84^ab	3.02±0.88^ab	6.62±2.46^a	13.25±2.13^ab	2.84±0.55^ab	4.36±1.37	8.67±2.25^ab	2.53±0.62^ab
VCIND group	56	5.03±2.11^a	56.85±6.61^a	9.23±2.14^a	5.47±2.19^a	38.16±4.24^a	6.19±2.02^a	4.03±1.45	14.19±1.97^a	4.47±1.29^a
VaD group	47	3.67±0.79	76.68±5.89	18.14±7.52	3.81±0.56	49.38±3.77	13.46±6.20	3.14±0.37	20.66±3.46	9.92±5.77
F		15.045	16.757	19.884	24.671	15.466	13.881	1.664	8.787	10.176
P		0.033	0.027	0.019	0.001	0.029	0.020	0.173	0.041	0.026

Items	NCI group		VCIND group		VaD group
Items	r	P	r	P	r	P
BDNF	0.822	＜0.01	0.796	＜0.01	0.842	＜0.01
IL-18	-0.741	＜0.01	-0.761	＜0.01	-0.713	＜0.01
hs-CRP	-0.778	＜0.01	-0.729	＜0.01	-0.686	＜0.01

Items	Standard error	Wald	P	Odds ratio	95%CI
Infarct area	0.075	4.52	0.033	2.830	0.982-3.428
NIHSS	0.042	7.66	0.010	3.437	1.226-4.271
BDNF	0.029	5.71	0.067	1.826	1.698-2.567
IL-18	0.061	6.13	0.016	1.171	0.977-3.685
hs-CRP	0.016	4.42	0.004	1.357	2.446-6.997