急性缺血性卒中患者静脉溶栓后血清微小RNA-874-3p、微小RNA-181a-5p及Wnt/β-catenin信号通路与神经功能预后的关系

doi:10.3969/j.issn.1673-5765.2024.10.009

摘要/Abstract

摘要： 目的探讨急性缺血性卒中（acute ischemic stroke，AIS）患者静脉溶栓后血清微小RNA（microRNA，miRNA）-874-3p（miR-874-3p）、miRNA-181a-5p（miR-181a-5p）与Wnt/β-catenin信号通路和神经功能预后的关系。
方法前瞻性连续纳入2021年3月—2022年12月深圳市龙华区中心医院接受静脉溶栓治疗的AIS患者进入AIS组，选取同期体检健康者进入对照组。检测并比较两组血清miR-874-3p、miR-181a-5p及外周血单个核细胞（peripheral blood mononuclear cell，PBMC）中Wnt/β-catenin相对表达水平，采用Pearson相关性分析AIS患者血清miR-874-3p、miR-181a-5p表达与Wnt/β-catenin信号通路的相关性。所有AIS患者出院后均随访3个月，根据mRS评分将完成随访的患者分为神经功能预后良好组和神经功能预后不良组，比较两组患者血清miR-874-3p、miR-181a-5p相对表达水平。采用多因素logistic回归方程分析AIS患者神经功能预后的影响因素。
结果本研究中，AIS组纳入185例患者，平均（62.8±7.3）岁；对照组纳入65例体检健康者，平均（63.4±6.9）岁。与对照组相比，AIS组血清miR-874-3p（1.02±0.21 vs. 1.46±0.23，P<0.001）相对表达水平及PBMC中Wnt mRNA（2.41±0.64 vs. 4.59±1.13，P<0.001）、β-catenin mRNA（1.19±0.18 vs. 2.34±0.73，P<0.001）相对表达水平均低于对照组，血清miR-181a-5p（1.95±0.32 vs. 1.27±0.27，P<0.001）相对表达水平高于对照组；Pearson相关性分析显示，AIS患者血清miR-874-3p表达与PBMC中Wnt mRNA（r=0.562，P<0.001）、β-catenin mRNA（r=0.611，P<0.001）表达呈正相关，miR-181a-5p表达与PBMC中Wnt mRNA（r=-0.586，P<0.001）、β-catenin mRNA（r=-0.595，P<0.001）表达呈负相关。AIS组中，神经功能预后良好104例，预后不良81例，预后不良率为43.78%；神经功能预后不良组血清miR-874-3p相对表达水平显著低于神经功能预后良好组（0.79±0.20 vs. 1.20±0.22，P<0.001），miR-181a-5p相对表达水平显著高于神经功能预后良好组（2.26±0.31 vs. 1.71±0.24，P<0.001）；神经功能预后不良组年龄[（65.48±7.45）岁 vs.（62.29±7.21）岁，P=0.004]、发病至入院时间[（4.36±1.03）h vs.（3.79±1.15）h，P=0.001]、入院时NIHSS评分[（6.81±2.45）分 vs.（4.67±1.76）分，P<0.001]及Hcy水平[（13.34±4.12）μmol/L vs.（11.75±3.46）μmol/L，P=0.005]均高于神经功能预后良好组；多因素logistic回归结果显示，年龄偏高（OR 1.056，95%CI 1.005～1.108，P=0.029）、发病至入院时间延长（OR 1.125，95%CI 1.008～1.256，P=0.035）、入院时NIHSS评分高（OR 1.220，95%CI 1.093～1.362，P<0.001）、miR-874-3p低表达（OR 0.632，95%CI 0.498～0.803，P<0.001）及miR-181a-5p高表达（OR 1.506，95%CI 1.209～1.875，P<0.001）是导致AIS神经功能预后不良的危险因素。
结论 AIS组患者血清miR-874-3p表达下降，miR-181a-5p表达升高，均与Wnt/β-catenin信号通路相关，血清miR-874-3p、miR-181a-5p水平是患者神经功能预后的影响因素。

文章导读： 本研究证实了血清miR-874-3p、miR-181a-5p对AIS患者神经功能预后的预测价值，并初步探究其作用机制可能与Wnt/β-catenin信号通路有关，临床可基于此靶点改善AIS患者预后。

关键词: 急性缺血性卒中; 微小核糖核酸-874-3p; 微小核糖核酸-181a-5p; 果蝇无翅基因蛋白/β-连环蛋白信号通路; 神经功能; 预后

Abstract: Objective To investigate the relationship between serum microRNA-874-3p (miR-874-3p),
microRNA-181a-5p (miR-181a-5p), Wnt/β-catenin signaling pathway and neurological function prognosis in patients with acute ischemic stroke (AIS).
Methods AIS patients who received intravenous thrombolytic therapy in Shenzhen Longhua District Central Hospital from March 2021 to December 2022 were prospectively included into the AIS group, and healthy subjects during the same period were selected into the control group. The relative expression levels of serum miR-874-3p, miR-181a-5p and peripheral blood mononuclear cell (PBMC) determination of Wnt/β-catenin were detected and compared between the two groups. Pearson correlation was used to analyze the correlation between the expression of miR-874-3p and miR-181a-5p in serum and the Wnt/β-catenin signaling pathway in AIS patients. All AIS patients were followed up for 3 months after discharge. Patients who completed follow-up were divided into the good neurological function prognosis group and the poor neurological function prognosis group based on the mRS score. The relative expression levels of miR-874-3p and miR-181a-5p were compared between the two groups. Multivariate logistic regression equation was used to analyze the factors affecting the prognosis of neurological function in AIS patients.
Results In this study, 185 patients were included in the AIS group, with an average age of (62.8±7.3) years. The control group included 65 healthy subjects with an average age of (63.4±6.9) years. Compared with the control group, the relative expression levels of miR-874-3p in serum (1.02±0.21 vs. 1.46±0.23, P<0.001) and Wnt mRNA (2.41±0.64 vs. 4.59±1.13, P<0.001), β-catenin mRNA in PBMC (1.19±0.18 vs. 2.34±0.73, P<0.001) in the AIS group were lower than those in the control group. The relative expression level of miR-181a-5p (1.95±0.32 vs. 1.27±0.27, P<0.001) was higher than that of the control group. Pearson correlation analysis showed that the expression of serum miR-874-3p was positively correlated with the expression of Wnt mRNA (r=0.562, P<0.001) and β-catenin mRNA (r=0.611, P<0.001) in PBMC, while the expression of miR-181a-5p was negatively correlated with the expression of Wnt mRNA (r=-0.586, P<0.001) and β-catenin mRNA (r=-0.595, P<0.001) in PBMC in AIS patients. In the AIS group, there were 104 patients with good neurological function prognosis and 81 patients with poor neurological function prognosis. The rate of poor neurological function prognosis was 43.78%. The relative expression level of miR-874-3p in serum in the poor neurological function prognosis group was significantly lower than that in the good neurological function prognosis group (0.79±0.20 vs. 1.20±0.22, P<0.001). The relative expression level of miR-181a-5p was significantly higher than that of the good neurological function prognosis group (2.26±0.31 vs. 1.71±0.24, P<0.001). In the poor neurological function prognosis group, age [(65.48±7.45) years vs. (62.29±7.21) years, P=0.004], time from onset to admission[(4.36±1.03) h vs. (3.79±1.15) h, P=0.001], the NIHSS score [(6.81±2.45) points vs. (4.67±1.76) points, P<0.001] and serum Hcy levels [(13.34±4.12) μmol/L vs. (11.75±3.46) μmol/L, P=0.005] were significantly higher than those in the good neurological function prognosis group. Multivariate logistic regression results showed that older age (OR 1.056, 95%CI 1.005-1.108, P=0.029), extend time from onset to admission (OR 1.125, 95%CI 1.008-1.256, P=0.035), high NIHSS score (OR 1.220, 95%CI 1.093-1.362, P<0.001), low expression of miR-874-3p (OR 0.632, 95%CI 0.498-0.803, P<0.001), and high expression of miR-181a-5p (OR 1.506, 95%CI 1.209-1.875, P<0.001) were risk factors for poor prognosis of AIS neurological function.
Conclusions The expression of serum miR-874-3p decreased and miR-181a-5p increased in AIS patients, both of which were related to the Wnt/β-catenin signaling pathway. The levels of serum miR-874-3p and miR-181a-5p were influencing factors for the prognosis of neurological function in patients.

Key words: Acute ischemic stroke; Microribonucleic acid-874-3p; Microribonucleic acid-181a-5p; Drosophila wingless gene protein/β-linked protein signaling pathway; Neurological function; Prognosis

中图分类号:

陈绪斌, 肖炜婷, 岳喜峰, 何能清, 曾小辉. 急性缺血性卒中患者静脉溶栓后血清微小RNA-874-3p、微小RNA-181a-5p及Wnt/β-catenin信号通路与神经功能预后的关系[J]. 中国卒中杂志, 2024, 19(10): 1162-1169.

CHEN Xubin, XIAO Weiting, YUE Xifeng, HE Nengqing, ZENG Xiaohui. Relationship between Serum MicroRNA-874-3p, MicroRNA-181a-5p, Wnt/β-catenin Signaling Pathway and Neurological Function Prognosis in Patients with Acute Ischemic Stroke after Intravenous Thrombolysis[J]. Chinese Journal of Stroke, 2024, 19(10): 1162-1169.

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