急性脑梗死患者血浆LncRNA CEBPA-AS1、miR-139-5p表达及与认知功能障碍的相关性分析

doi:10.11958/20241422

摘要/Abstract

摘要：

目的检测急性脑梗死（ACI）患者血浆长链非编码RNA（LncRNA）CCAAT增强子结合蛋白α反义1（CEBPA-AS1）与miR-139-5p的水平，并探讨二者与认知功能障碍的关系。方法选取132例ACI患者为研究对象，利用蒙特利尔认知评估量表（MoCA）将患者分为认知功能障碍组（63例）和认知功能正常组（69例）。比较2组一般资料；采用实时荧光定量PCR（qRT-PCR）法检测患者血浆LncRNA CEBPA-AS1、miR-139-5p水平；Pearson法分析血浆LncRNA CEBPA-AS1与miR-139-5p的相关性；多因素Logistic回归分析ACI患者发生认知功能障碍的影响因素；受试者工作特征（ROC）曲线评估血浆LncRNA CEBPA-AS1和miR-139-5p水平对认知功能障碍的诊断价值。结果与认知功能正常组相比，认知功能障碍组血浆LncRNA CEBPA-AS1水平升高，miR-139-5p水平降低（P<0.05）；相关性分析显示，LncRNA CEBPA-AS1水平与miR-139-5p水平呈负相关（r=-0.462，P<0.01）；多因素分析显示，受教育程度高中及以下、血浆miR-139-5p水平降低、LncRNA CEBPA-AS1水平升高是ACI患者发生认知功能障碍的危险因素（P<0.05）；LncRNA CEBPA-AS1和miR-139-5p诊断ACI患者发生认知功能障碍的曲线下面积（AUC）分别为0.865、0.798，二者联合诊断的效能（AUC=0.912）优于单一指标。结论 ACI合并认知功能障碍患者血浆LncRNA CEBPA-AS1水平升高、miR-139-5p水平降低，二者均是ACI患者发生认知功能障碍的影响因素，且联合诊断的效能较高。

关键词: 认知功能障碍, 脑梗死, 急性病, 长链非编码RNA CEBPA-AS1, 微小RNA-139-5p

Abstract:

Objective To detect levels of plasma long non coding RNA (lncRNA) CCAAT enhancer binding protein alpha antisense 1 (CEBPA-AS1) and microRNA-139-5p (miR-139-5p) in patients with acute cerebral infarction (ACI), and to explore their relationship with cognitive dysfunction in ACI patients.Methods A total of 132 ACI patients treated in our hospital were included for the study. The Montreal Cognitive Assessment Scale (MoCA) was used to evaluate the cognitive function of ACI patients, and they were diveded into the cognitive dysfunction group (n=63) and the normal cognitive function group (n=69). The general data of the two groups were compared. The qRT-PCR method was applied to measure plasma levels of lncRNA CEBPA-AS1 and miR-139-5p in ACI patients. Pearson method was applied to analyze the correlation between plasma lncRNA CEBPA-AS1 and miR-139-5p in ACI patients. Multivariate Logistic regression was applied to analyze factors influencing cognitive dysfunction in ACI patients. Receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic value of plasma lncRNA CEBPA-AS1 and miR-139-5p for cognitive dysfunction in ACI patients.Results Compared with the normal cognitive function group, the plasma lncRNA CEBPA-AS1 was higher and the miR-139-5p was lower in the cognitive dysfunction group (P<0.05). Correlation analysis showed that there was a negative correlation between lncRNA CEBPA-AS1 and miR-139-5p (r=-0.462, P<0.01). Multivariate analysis showed that high school education or below, decreased plasma miR-139-5p, and increased lncRNA CEBPA-AS1 were risk factors for cognitive dysfunction in ACI patients (P<0.05). The area under the curve (AUC) of lncRNA CEBPA-AS1 and miR-139-5p in the diagnosis of cognitive dysfunction in ACI patients was 0.865 and 0.798, respectively. The combined diagnostic efficacy of the two (AUC=0.912) was better than single index.Conclusion The plasma lncRNA CEBPA-AS1 is increased and the plasma miR-139-5p is decreased in patients with ACI combined with cognitive dysfunction, and both are influencing factors for cognitive dysfunction in ACI patients, and the combined diagnostic efficacy is high.

Key words: cognitive dysfunction, cerebral infarction, acute disease, long non coding RNA CEBPA-AS1, miR-139-5p

中图分类号:

R741

图/表 7

参考文献 19

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组别		n	年龄/岁			性别				受教育程度
组别		n	年龄/岁			男		女		大学及以上				高中及以下
认知功能正常组		69	60.90±8.72			36（52.17）		33（47.83）		45（65.22）				24（34.78）
认知功能障碍组		63	62.64±8.81			32（50.79）		31（49.21）		13（20.63）				50（79.37）
t或χ²			1.139			0.025					26.572^＊＊
组别	基础病史								饮酒			吸烟	MoCA评分/分
组别	高血压				糖尿病		冠心病		饮酒			吸烟	MoCA评分/分
认知功能正常组	37（53.62）				39（56.52）		45（65.22）		13（18.84）			32（46.38）	28.25±1.72
认知功能障碍组	36（57.14）				38（60.32）		43（68.25）		17（26.98）			27（42.86）	20.14±2.31
t或χ²	0.165			0.195			0.137		1.244			0.165	23.006^＊＊

组别		n	年龄/岁			性别				受教育程度
组别		n	年龄/岁			男		女		大学及以上				高中及以下
认知功能正常组		69	60.90±8.72			36（52.17）		33（47.83）		45（65.22）				24（34.78）
认知功能障碍组		63	62.64±8.81			32（50.79）		31（49.21）		13（20.63）				50（79.37）
t或χ²			1.139			0.025					26.572^＊＊
组别	基础病史								饮酒			吸烟	MoCA评分/分
组别	高血压				糖尿病		冠心病		饮酒			吸烟	MoCA评分/分
认知功能正常组	37（53.62）				39（56.52）		45（65.22）		13（18.84）			32（46.38）	28.25±1.72
认知功能障碍组	36（57.14）				38（60.32）		43（68.25）		17（26.98）			27（42.86）	20.14±2.31
t或χ²	0.165			0.195			0.137		1.244			0.165	23.006^＊＊

基因名称	引物序列（5′→3′）	产物大小/ bp
LncRNA CEBPA-AS1	上游：GCTTCGTTTTCGGTCCAGA	152
	下游：CCCTCCACAGGTGAATGCTAT	152
GAPDH	上游：GCTGCAGAGGTCCGAAGAA	136
	下游：GCTGCAGAAGGTCCGAAGAA	136
miR-139-5p	上游：CATCGCGCATGCTAGCTAGACC	58
	下游：ATACGGCAACGTACGCGACGCATA	58
U6	上游：GCTGGACTCTAGGGTGCAAG	141
	下游：GAGCATACCAGGTGGTAGTAG	141

基因名称	引物序列（5′→3′）	产物大小/ bp
LncRNA CEBPA-AS1	上游：GCTTCGTTTTCGGTCCAGA	152
	下游：CCCTCCACAGGTGAATGCTAT	152
GAPDH	上游：GCTGCAGAGGTCCGAAGAA	136
	下游：GCTGCAGAAGGTCCGAAGAA	136
miR-139-5p	上游：CATCGCGCATGCTAGCTAGACC	58
	下游：ATACGGCAACGTACGCGACGCATA	58
U6	上游：GCTGGACTCTAGGGTGCAAG	141
	下游：GAGCATACCAGGTGGTAGTAG	141

组别	n	LncRNA CEBPA-AS1	miR-139-5p
认知功能正常组	69	1.02±0.04	0.99±0.03
认知功能障碍组	63	1.26±0.28	0.82±0.16
t		7.044^＊＊	8.664^＊＊