血清miR-125b-5p在急性缺血性脑卒中患者中的表达及其与Hcy、Hs-CRP及MMP-9的相关性

Expression of serum miR-125b-5p in patients with acute ischemic stroke and its correlation with Hcy, Hs-CRP and MMP-9

目的:探讨急性缺血性脑卒中(acute ischemic stroke,AIS)患者血清miR-125b-5p的表达与同型半胱氨酸(homocysteine,Hcy)、超敏C反应蛋白(hypersensitive C-reactive protein,Hs-CRP)及基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)的相关性,为AIS的诊治提供依据。方法:选取2016年1月至2019年5月海南省第三人民医院收治的174例AIS,采用美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分分为轻度组(n=51,NIHSS评分<5分)、中度组(n=79,5分≤NIHSS评分≤20分)和重度组(n=44,NIHSS评分>20分)。另选择65例健康体检正常者作为对照组。采用实时荧光定量PCR检测各组血清miR-125b-5p表达水平。应用ROC曲线分析血清miR-125b-5p、Hcy、Hs-CRP及MMP-9水平对AIS诊断的价值,Pearson相关分析AIS患者血清miR-125b-5表达水平与Hcy、Hs-CRP及MMP-9的相关性。结果:AIS组血清miR-125b-5p[(2.74±0.95)vs.(0.68±0.13)]、Hcy[(19.26±5.37)μmol/L vs.(5.84±1.20)μmol/L]、Hs-CRP[(6.85±1.73)mg/L vs.(1.04±0.28)mg/L]及MMP-9[(150.75±30.82)μg/L vs.(78.62±11.40)μg/L]水平明显高于对照组(t=14.217,P=0.000;t=13.475,P=0.000;t=10.624,P=0.000;t=9.806,P=0.000)。重度组血清miR-125b-5 [(4.10±1.18)vs.(2.62±0.84)、(1.70±0.53)]、Hcy[(28.35±6.80)μmol/L vs.(18.42±4.93)μmol/L、(11.50±3.27)μmol/L]、Hs-CRP[(11.92±3.25)mg/L vs.(6.14±1.57)mg/L、(2.76±0.63)mg/L)]及MMP-9[(225.80±47.63)μg/L vs.(142.52±26.80)μg/L、(86.50±12.62)μg/L)]水平均明显高于中度组和轻度组(F=10.845,P=0.000;F=8.716,P=0.000;F=5.184,P=0.003;F=4.972,P=0.010)。血清miR-125b-5p诊断AIS的AUC(95%CI)为0.846(0.787~0.903),明显高于Hcy[0.754(0.693~0.812)]、Hs-CRP[0.728(0.672~0.788)]及MMP-9[0.695(0.634~0.753)],其最佳临界值取2.10时,敏感度和特异度分别为88.0%和80.7%。相关分析显示,AIS患者血清miR-125b-5p表达水平与Hcy、Hs-CRP及MMP-9均呈正相关(r=0.836、0.745、0.702,P<0.01)。结论:血清miR-125b-5p表达水平在AIS患者中明显升高,且与Hcy、Hs-CRP及MMP-9水平相关,有望作为AIS诊断的生物标志物。

Objective:To investigate the correlation between the expression of serum miR-125 b-5 p and homocysteine(Hcy),hypersensitive C-reactive protein(Hs-CRP)and matrix metalloproteinase-9(MMP-9)in elderly patients with acute ischemic stroke(AIS),and to provide evidence for the diagnosis and treatment of AIS. Methods:The study involved in 174 cases of AIS who admitted to the Third People’s Hospital of Hainan Province from January 2016 to May 2019. The National Institutes of Health Stroke Scale(NIHSS)score were used to divide the patients into mild group(n=51,NIHSS score<5 points),moderate group(n=79,5 points≤NIHSS score≤20 points),and severe group(n=44,NIHSS score>20 points). Another 65 healthy subjects were selected as control group. Real-time fluorescent quantitative PCR was used to detect the expression of serum miR-125 b-5 p in each group. The diagnostic value of serum levels of miR-125 b-5 p,Hcy,Hs-CRP and MMP-9 for AIS patients were analyzed by ROC curve. Pearson correlation analysis was conducted to analyze the correlation of serum levels of miR-125 b-5 p with Hcy,Hs-CRP and MMP-9 in AIS patients. Results:The levels of serum mi R-125 b-5 p[(2.74±0.95)vs.(0.68±0.13)],Hcy [(19.26 ±5.37) μmol/L vs.(5.84 ±1.20) μmol/L],Hs-CRP[(6.85±1.73)mg/L vs.(1.04±0.28)mg/L] and MMP-9[(150.75±30.82)μg/L vs.(78.62±11.40)μg/L] in AIS group were significantly higher than those in control group(t=14.217,P=0.000;t=13.475,P=0.000;t=10.624,P=0.000;t=9.806,P=0.000). The serum levels of mi R-125 b-5[(4.10±1.18)vs.(2.62±0.84)and(1.70±0.53)],Hcy[(28.35±6.80)μmol/L vs.(18.42±4.93)μmol/L and(11.50±3.27)μmol/L],Hs-CRP[(11.92±3.25)mg/L vs.(6.14±1.57)mg/L and(2.76±0.63)mg/L] and MMP-9[(225.80±47.63)μg/L vs.(142.52±26.80)μg/L and(86.50±12.62)μg/L] in severe group were significantly higher than those in moderate group and mild group(F=10.845,P=0.000,F=8.716,P=0.000,F=5.184,P=0.003,F=4.972,P=0.010). The AUC(95%CI)of serum mi R-125 b-5 p in diagnosis of elderly AIS was 0.846(0.787-0.903),which was significantly higher than that of Hcy [0.754(0.693-0.812)],Hs-CRP [0.728(0.672-0.788)] and MMP-9 [0.695(0.634-0.753)]. When the optimal critical value of mi R-125 b-5 p was 2.10,the sensitivity and specificity were 88.0% and 80.7%. Relevant analysis showed that serum levels of mi R-125 b-5 p were positively correlated with levels of Hcy,Hs-CRP and MMP-9 in elderly patients with AIS(r=0.836,0.745,0.702,P<0.01). Conclusion:Serum mi R-125 b-5 p expression level is significantly increased in AIS patients,and correlated with Hcy,Hs-CRP and MMP-9 levels,which may be used as biomarkers for the diagnosis of AIS in elderly patients.