血浆外泌体miR-124-3p对慢性脑缺血风险预测价值的研究

Predictive value of plasma exosomal miR-124-3p for the risk of chronic cerebral hypoperfusion

目的:探讨血浆外泌体microRNA(miR)-124-3p对慢性脑缺血(CCH)的风险预测价值。方法:病例对照研究。回顾性纳入30例2022年3月至2022年6月在四川省医学科学院四川省人民医院神经科门诊根据动脉自旋标记(ASL)诊断为CCH的患者(CCH组)和30名健康志愿者(对照组)。比较两组的年龄、性别、吸烟史、饮酒史、糖尿病史、高血压、高脂血症病史、尿酸、空腹血糖、同型半胱氨酸和血浆外泌体miR-124-3p表达水平。分类变量的比较选择 χ2检验或Fisher精确检验进行分析。连续变量数据遵循正态分布,通过两独立样本 t检验进行数据比较;非正态分布选择Mann-Whitney U检验进行两组间比较。脑血流量和外泌体miR-124-3p之间进行Pearson相关分析。采用二元多因素logistic回归分析来确定CCH的相关危险因素,并计算比值比( OR)和95%置信区间( CI)。 P<0.05为差异有统计学意义。 结果:两组在年龄[(64±8)比(60±8)岁]、性别(33.3% 比 30.0%)、吸烟史(20.0% 比 3.3%)、饮酒史(20.0% 比 6.7%)、糖尿病史(13.3% 比 13.3%)、高血压(53.3% 比 30.0%)、高脂血症史(46.7%比36.7%)、尿酸[(288±60)比(319±67)μmol/L]、空腹血糖[4.99(4.63,5.91)比5.28(5.09,6.05)mmol/L]和同型半胱氨酸[11.35(10.18,13.08)比11.00(9.78,13.03)μmol/L]差异无统计学意义(均 P>0.05)。CCH组的血浆外泌体miR-124-3p水平明显高于对照组[13.08(8.59,21.55)比 2.85(1.44,5.10), U=169.50, P<0.001]。Pearson相关分析显示,在CCH患者的低灌注区,血浆外泌体miR-124-3p水平与脑血流量负相关( r=-0.932, P<0.001)。多因素logistic回归分析显示,血浆外泌体miR-124-3p与CCH的风险独立相关( OR=1.169,95% CI 1.063~1.286, P=0.001)。 结论:血浆外泌体miR-124-3p是CCH的独立危险因素,且与低灌注区域脑血流量呈负相关。血浆外泌体miR-124-3p可作为CCH风险预测的一个有效的生物标志物。

ObjectiveTo investigate the predictive value of plasma exosomal microRNA(miR)-124-3p in the risk of chronic cerebral hypoperfusion(CCH).MethodsA case-control study.Thirty patients who were diagnosed with CCH(CCH group)based on cranial artery spin labeling(ASL)in the neurology outpatient clinic of Sichuan Provincial People′s Hospital from March 2022 to June 2022 and 30 healthy volunteers(control group)were included.Age,gender,smoking history,alcohol consumption history,diabetes history,hypertension,hyperlipidemia history,uric acid,fasting blood glucose,homocysteine and plasma exosomal miR-124-3p expression level were compared between the two groups.Comparisons of categorical variables were analyzed by eitherχ2 test or Fisher′s exact test.If the data of continuous variables followed a normal distribution,they were expressed as mean±standard deviation(SD)and compared by t-test for two independent samples;otherwise,the data were expressed as M(Q1,Q3),and analyzed by Mann-Whitney U test for comparison between two groups.The correlation between cerebral blood flow and exosomal miR-124-3p levels was analyzed by Pearson′s correlation.Binary multifactorial logistic regression analysis was used to determine the risk factors associated with CCH,and corresponding odds ratios(OR)and 95%confidence intervals(CI)were calculated.P<0.05 was considered significant.ResultsThere was no significant difference in age(64±8 vs.60±8 years old),gender(33.3%vs.30.0%),history of smoking(20.0%vs.3.3%),alcohol consumption(20.0%vs.6.7%),diabetes mellitus(13.3%vs.13.3%),hypertension(53.3%vs.30.0%),history of hyperlipidemia(46.7%vs.36.7%),uric acid(288±60 vs.319±67μmol/L),and fasting glucose[4.99(4.63,5.91)vs.5.28(5.09,6.05)mmol/L]and homocysteine[11.35(10.18,13.08)vs.11.00(9.78,13.03)μmol/L]between the CCH and control groups(P>0.05).Plasma exosomal miR-124-3p expression was significantly higher in the CCH group than in the control group[13.08(8.59,21.55)vs.2.85(1.44,5.10),respectively;U=169.50,P<0.001].Pearson′s correlation test showed that the level of exosomal miR-124-3p was negatively correlated with cerebral blood flow in the hypoperfused region in patients with CCH(r=-0.932,P<0.001).Multi-factor logistic regression analysis showed that plasma exosomal miR-124-3p was independently associated with the risk of CCH(OR=1.169,95%CI 1.063-1.286,P=0.001).ConclusionsThe expression of plasma exosomal miR-124-3p is negatively correlated with cerebral blood flow in areas of low perfusion and is an independent risk factor for CCH.Plasma exosomal miR-124-3p may thus serve as a valid biomarker for CCH risk prediction.