目的:探讨血清脑源性神经营养因子(BDNF)水平与脑源性神经营养因子(BDNF)、白细胞介素-18(IL-18)和超敏C反应蛋白(hs-CRP)在急性脑梗死和血管性认知障碍(VCI)患者中,为早期预防VCI提供临床依据。
方法:以晋城市人民医院神经内科2019年5月至2020年4月收治的160例急性脑梗死患者为研究对象,根据是否合并认知障碍分为三组。包括无认知障碍组(NCI,57例),血管性认知障碍无痴呆组(VCIND,56例)和血管性痴呆组(VaD,47例)。采用蒙特利尔认知评估量表(MoCA)评价所有患者的认知功能。美国国立卫生研究院卒中量表(NIHSS)用于评估神经功能缺损程度(mid-,moderate-,严重神经功能缺损组)。通过Pullicino方法计算梗死面积(小,middle-,大梗死组)。酶联免疫吸附试验(ELISA)检测血清BDNF和IL-18水平,在急性期(0-7d)通过免疫比浊法测量血清hs-CRP水平,恢复期(15-30d)和脑梗死后6个月。不同程度的神经功能缺损和不同大小的梗死对BDNF,观察IL-18和hs-CRP。血清BDNF水平,IL-18和hs-CRP在三组急性,比较康复期和6个月脑梗死,并分析其与VCI的相关性。
结果:轻度神经功能缺损组和小梗死组的血清BDNF水平和MoCA评分明显高于中度和重度缺损组,中大梗死组,分别为(P<0.05)。他们的IL-18和hs-CRP水平明显低于中度和重度缺陷组。中大梗死组,分别为(P<0.05)。NCI组血清BDNF水平,VCIND组和VaD组在急性期,恢复期和脑梗死后6个月出现明显下降,急性期和恢复期差异均有统计学意义(P<0.05)。急性期IL-18和hs-CRP水平,恢复期和脑梗死后6个月呈明显上升趋势,差异有统计学意义(P<0.05)。相关分析显示,BDNF水平与MoCA评分呈正相关,与认知障碍严重程度呈负相关;IL-18和hs-CRP表达水平与MoCA评分呈负相关,与认知障碍严重程度呈正相关。
结论:血清BDNF,IL-18和hs-CRP参与了急性脑梗死患者VCI发生发展的病理过程。BDNF对VCI有保护作用,而IL-18和hs-CRP可引起严重的认知功能障碍。急性缺血性脑梗死患者血清BDNF、IL-18和hs-CRP水平与认知功能障碍的严重程度密切相关,可作为VCI早期诊断的生物标志物。
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.
CONCLUSIONS: 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.