缺血性脑卒中患者和大鼠血清中天麻素原性神经营养因子浓度升高。

Increased serum concentrations of Mesencephalic astrocyte-derived neurotrophic factor in patients and rats with ischemic stroke.

机构信息

Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 150001, Harbin, Heilongjiang, China.

Department of Respiratory Medicine, The First Affiliated Hospital of Harbin Medical University, 150001, Harbin, Heilongjiang, China.

出版信息

J Stroke Cerebrovasc Dis. 2022 Nov;31(11):106752. doi: 10.1016/j.jstrokecerebrovasdis.2022.106752. Epub 2022 Sep 7.

DOI:10.1016/j.jstrokecerebrovasdis.2022.106752

PMID:36087374

Abstract

OBJECTIVES

Although Mesencephalic astrocyte-derived neurotrophic factor (MANF) shows protection in multiple cells, the role of circulating MANF in patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA) remains unclear. Here, we aimed to explore the value of circulating MANF levels in cerebral ischemic events.

MATERIALS AND METHODS

Using a rat cerebral ischemic model, MANF expression in ischemic brains and serum was detected. 50 AIS patients, 56 TIA patients and 48 controls were enrolled, and MANF mRNA, inflammatory cytokines and MANF concentrations in serum and different blood cell types were detected. The National Institutes of Health Stroke Scale (NIHSS) score and Alberta Stroke Program Early CT Score (ASPECTS) were used to evaluate stroke severity. Cerebrovascular recurrence within 90 d was documented during TIA follow-up.

RESULTS

MANF expression increased at 2h, peaking at 24h and decreased to baseline at 7d in rat ischemic brains and serum. Serum MANF concentrations increased at 24h and 7d in AIS patients compared to controls and were correlated with NIHSS score, ASPECTS and inflammatory cytokines. MANF protein was present in blood cells, while MANF mRNA levels did not differ between AIS patients and controls. MANF levels revealed a good value to diagnose TIA with area under the curve (AUC) of 0.949 (95% CI: 0.9093-0.9892). MANF levels were lower in TIA patients with recurrence compared to non-recurrence patients. The AUC for MANF to predict a re-event was 0.80 (95% CI: 0.6746-0.9282).

CONCLUSIONS

Serum MANF levels correlate with neuroprotection, stroke severity, inflammation, and TIA recurrence.

摘要

目的

间脑星形胶质细胞衍生神经营养因子（MANF）在多种细胞中均表现出保护作用，但循环 MANF 在急性缺血性脑卒中（AIS）和短暂性脑缺血发作（TIA）患者中的作用尚不清楚。本研究旨在探讨循环 MANF 水平在脑缺血事件中的价值。

材料和方法

采用大鼠脑缺血模型，检测缺血脑组织和血清中 MANF 的表达。纳入 50 例 AIS 患者、56 例 TIA 患者和 48 例对照者，检测血清和不同血细胞类型中的 MANF mRNA、炎症细胞因子和 MANF 浓度。采用国立卫生研究院卒中量表（NIHSS）评分和 Alberta 卒中项目早期 CT 评分（ASPECTS）评估卒中严重程度。在 TIA 随访期间记录 90d 内的脑血管事件复发情况。

结果

大鼠缺血脑组织和血清中 MANF 表达于 2h 升高，24h 达峰值，7d 降至基线。与对照组相比，AIS 患者血清 MANF 浓度于 24h 和 7d 升高，与 NIHSS 评分、ASPECTS 和炎症细胞因子相关。MANF 蛋白存在于血细胞中，而 AIS 患者与对照组之间 MANF mRNA 水平无差异。MANF 水平对 TIA 的诊断具有良好的价值，曲线下面积（AUC）为 0.949（95%CI：0.9093-0.9892）。与无复发患者相比，复发的 TIA 患者 MANF 水平较低。MANF 预测再发事件的 AUC 为 0.80（95%CI：0.6746-0.9282）。