老年阿尔茨海默病患者血清中TNF-α、M-CSF及miR-181a的表达水平及临床应用价值

Expression levels and clinical application value of TNF-α,M-CSF and miR-181a in serum of elderly AD patients

目的观察阿尔茨海默病(Alzheimer′s disease,AD)患者血清肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、巨噬细胞集落刺激因子(macrophage colony stimulating factor,M-CSF)及微小RNA(microRNA,miR)-181a表达及诊断价值。方法选取我院诊治的AD患者140例为研究对象(AD组),根据临床痴呆量表评分分为轻度组52例,中度组49例,重度组39例,以同期健康查体的50例健康人为对照组。应用实时荧光定量聚合酶链式反应(polymerase chain reaction,PCR)法检测血清miR-181a相对表达量,采用酶联免疫吸附实验检测血清TNF-α、M-CSF水平。血清TNF-α、M-CSF及miR-181a的相关性采用Pearson相关分析。受试者工作曲线分析血清TNF-α、M-CSF及miR-181a表达对AD的诊断价值。结果AD组血清TNF-α、M-CSF及miR-181a表达水平均明显高于对照组(t=49.291、30.485、28.313,P<0.05)。轻、中、重度组间血清TNF-α、M-CSF及miR-181a表达差异有统计学意义(P<0.05)。AD患者血清TNF-α与M-CSF、miR-181a表达呈显著正相关(r=0.524、0.610,P<0.05),M-CSF与miR-181a表达呈显著正相关(r=0.498,P<0.05)。血清TNF-α>27.18 ng/L、血清M-CSF>635.81 ng/L及血清miR-181a>1.83为影响AD发生的危险因素。血清TNF-α、M-CSF、miR-181a及联合检测的曲线下面积分别为0.741(95%CI:0.684~0.789)、0.693(95%CI:0.630~0.757)、0.727(95%CI:0.682~0.774)及0.862(95%CI:0.818~0.899),联合检测诊断AD的曲线下面积大于TNF-α、M-CSF及miR-181a单独诊断(Z=3.357、5.894、4.911,P<0.05)。结论AD患者血清TNF-α、M-CSF及miR-181a表达升高,三者升高程度是AD发生的独立危险因素,三者联合检测对AD的诊断具有较高的价值。

Objective To observe the expression of tumor necrosis factor-α(TNF-α),macrophage colony stimulating factor(M-CSF)and microRNA(miR)-181a in serum of patients with Alzheimer's disease(AD)and their diagnostic value.Methods A total of 140 AD patients diagnosed and treated in our hospital were selected as the research subjects(AD group),and they were divided into the mild group(n=52),the moderate group(n=49),and the severe group(n=39)according to the clinical dementia scale,and 50 healthy people who underwent physical examination during the same period were used as the control group.The relative expression of serum miR-181a was detected by real-time fluorescence quantitative PCR(RT-qPCR),and the levels of serum TNF-αand M-CSF were detected by enzyme-linked immunosorbent assay(ELISA).The correlation of serum TNF-α,M-CSF and miR-181a was analyzed by Pearson correlation.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of serum TNF-α,M-CSF and miR-181a expression in AD.Results The expression levels of serum TNF-α,M-CSF and miR-181a in AD group were significantly higher than those in control group(t=49.291,30.485,28.313,all P<0.05).There were statistically significant differences in the expressions of serum TNF-α,M-CSF and miR-181a among the mild,moderate and severe groups(all P<0.05).Serum TNF-αin AD patients was significantly and positively correlated with the expressions of M-CSF and miR-181a(r=0.524,0.610,both P<0.05),and M-CSF was significantly and positively correlated with the expression of miR-181a(r=0.498,P<0.05).Serum TNF-α>27.18 ng/L,serum M-CSF>635.81 ng/L and serum miR-181a>1.83 were the risk factors of AD.The areas under the ROC curve(AUC)of serum TNF-α,M-CSF,miR-181a and joint testing were 0.741(95%CI:0.684-0.789),0.693(95%CI:0.630-0.757),0.727(95%CI:0.682-0.774)respectively,and 0.862(95%CI:0.818-0.899),and the AUC of combined detection in diagnosing AD was greater than that of TNF-α,M-CSF and miR-181a alone in diagnosis(Z=3.357,5.894,4.911,all P<0.05).Conclusion The expression of serum TNF-α,M-CSF and miR-181a in AD patients is increased,and the increased levels of the three are independent risk factors for AD,and the combined detection of the three has high value in the diagnosis of AD.