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急性缺血性脑卒中患者3年期间CDC42的纵向变化:与CD4 T细胞、疾病严重程度及预后的相关性

Longitudinal Variations of CDC42 in Patients With Acute Ischemic Stroke During 3-Year Period: Correlation With CD4 T Cells, Disease Severity, and Prognosis.

作者信息

Cheng Xiao, Ye Jianxin, Zhang Xiaolei, Meng Kun

机构信息

Department of Neurology, ShanXi Province People's Hospital of Shanxi Medical University, Taiyuan, China.

Shanxi Key Laboratory of Brain Disease Control, Shanxi Provincial People's Hospital, Taiyuan, China.

出版信息

Front Neurol. 2022 Apr 25;13:848933. doi: 10.3389/fneur.2022.848933. eCollection 2022.

Abstract

OBJECTIVE

Cell division cycle 42 (CDC42) modulates CD4 T-cell differentiation, blood lipids, and neuronal apoptosis and is involved in the pathogenesis of acute ischemic stroke (AIS); however, the clinical role of CDC42 in AIS remains unanswered. This study aimed to evaluate the expression of CDC42 in a 3-year follow-up and its correlation with disease severity, T helper (Th)1/2/17 cells, and the prognosis in patients with AIS.

METHODS

Blood CDC42 was detected in 143 patients with AIS at multiple time points during the 3-year follow-up period and in 70 controls at admission by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, blood Th1, Th2, and Th17 cells and their secreted cytokines (interferon-γ (IFN-γ), interleukin-4 (IL-4), and interleukin-17A (IL-17A)) in patients with AIS were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively.

RESULTS

Compared with controls ( < 0.001), CDC42 was reduced in patients with AIS. CDC42 was negatively correlated with the National Institutes of Health Stroke Scale (NIHSS) score ( < 0.001), whereas, in patients with AIS (all < 0.050), it was positively associated with Th2 cells and IL-4 but negatively correlated with Th17 cells and IL-17A. CDC42 was decreased from admission to 3 days and gradually increased from 3 days to 3 years in patients with AIS (<0.001). In a 3-year follow-up, 24 patients with AIS recurred and 8 patients died. On the 3rd day, 7th day, 1st month, 3rd month, 6th month, 1st year, 2nd year, and 3rd year, CDC42 was decreased in recurrent patients than that in non-recurrent patients (all < 0.050). CDC42 at 7 days ( = 0.033) and 3 months ( = 0.023) was declined in reported deceased patients than in survived patients.

CONCLUSION

CDC42 is used as a biomarker to constantly monitor disease progression and recurrence risk of patients with AIS.

摘要

目的

细胞分裂周期蛋白42(CDC42)可调节CD4 T细胞分化、血脂及神经元凋亡,参与急性缺血性脑卒中(AIS)的发病机制;然而,CDC42在AIS中的临床作用仍不明确。本研究旨在评估AIS患者3年随访期间CDC42的表达情况及其与疾病严重程度、辅助性T(Th)1/2/17细胞和预后的相关性。

方法

采用逆转录定量聚合酶链反应(RT-qPCR)在143例AIS患者3年随访期间的多个时间点及70例对照组入院时检测血液中的CDC42。此外,分别采用流式细胞术和酶联免疫吸附测定(ELISA)检测AIS患者血液中的Th1、Th2和Th17细胞及其分泌的细胞因子(干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)和白细胞介素-17A(IL-17A))。

结果

与对照组相比(<0.001),AIS患者的CDC42降低。CDC42与美国国立卫生研究院卒中量表(NIHSS)评分呈负相关(<0.001),而在AIS患者中(均<0.050),它与Th2细胞和IL-4呈正相关,但与Th17细胞和IL-17A呈负相关。AIS患者从入院到第3天CDC42降低,从第3天到3年逐渐升高(<0.001)。在3年随访中,24例AIS患者复发,8例死亡。在第3天、第7天、第1个月、第3个月、第6个月、第1年、第2年和第3年,复发患者的CDC42低于未复发患者(均<0.050)。报告的死亡患者在第7天(=0.033)和第3个月(=0.023)时的CDC42低于存活患者。

结论

CDC42可作为一种生物标志物,持续监测AIS患者的疾病进展和复发风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef56/9081787/af6d27c15ec8/fneur-13-848933-g0001.jpg

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