李晓庆.脑脊液中Na+-K+-Cl-协同转运蛋白1启动子甲基化对重型颅脑损伤患者预后有评估价值[J].内科急危重症杂志,2023,29(4):316-319
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| DOI：10.11768/nkjwzzzz20230413 |
| 中文关键词: 重型颅脑损伤 Na+-K+-Cl-协同转运蛋白1 甲基化状态 预后 |
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| 中文摘要: |
| 摘要 目的：探讨重型颅脑损伤(sTBI)患者脑脊液中Na+K+Cl-协同转运蛋白1（NKCC1）基因启动子甲基化的临床意义。方法:招募92例sTBI患者，根据格拉斯哥预后量表（GOS）将患者分为预后良好组（GOS>3分）63例与预后不良组（GOS≤3分）29例，选取同一时间段行腰椎内固定术后脑脊液漏的51例患者作为对照组。收集2组脑脊液样本，采用亚硫酸氢盐测序法(BSP)测定NKCC1启动子区域CpG位点的甲基化状态。采用Logistic回归分析影响sTBI患者预后的风险因素。采用受试者工作特征 (ROC）曲线评估启动子甲基化的预测价值。采用定量反转录聚合酶链式反应法检测NKCC1在sTBI患者脑脊液中mRNA的表达水平。采用Pearson相关系数对启动子甲基化水平与其mRNA 表达水平进行相关性分析。结果:预后不良组患者NKCC1的CpG_30.31、CpG_39.40.41位点的甲基化水平低于预后良好组（P均<0.05）。Logistic回归分析显示CpG_30.31、CpG_39.40.41位点甲基化水平是影响sTBI患者预后的独立风险因素（P均<0.05）。ROC曲线分析结果显示CpG_30.31、CpG_39.40.41位点甲基化水平预测sTBI患者预后的曲线下面积（AUC）为0.7085、0.7315（P=0.0014，0.0004）。NKCC1的CpG_30.31、CpG_39.40.41位点甲基化水平与NKCC1的mRNA水平呈负相关（r=-0.2574、-0.1328, P=0.0138、0.0325）。结论：NKCC1启动子甲基化状态对评估sTBI患者预后有价值。 |
| 英文摘要: |
| Abstract Objective: To investigate the methylation status and clinical significance of Na+K+Cl- cotransporter 1 (NKCC1) gene promoter in cerebrospinal fluid of patients with severe traumatic brain injury (sTBI). Methods: A total of 92 patients with sTBI were recruited and divided into the favorable prognosis group (GOS> 3 points) and poor prognosis group (GOS≤ 3 points) according to Glasgow Outcome Scale (GOS). A total of 51 patients with cerebrospinal fluid leakage after lumbar internal fixation were collected as controls. Cerebrospinal fluid samples from each group were collected. The methylation status of CpG sites in the promoter region of NKCC1 was determined by bisulfite sequencing (BSP). Logistic regression was used to analyze the risk factors affecting the prognosis of sTBI patients.The predictive value of promoter methylation was evaluated by using receiver operating characteristic (ROC) curves. The mRNA expression of NKCC1 in cerebrospinal fluid of sTBI patients was detected by qRT-PCR. The correlation between the methylation status of NKCC1 gene promoter and mRNA expression level was analyzed by Pearson correlation coefficient. Results: As compared with the good prognosis group, methylation levels of CpG_30.31 and CpG_39.40.41 in NKCC1 in the poor prognosis group were decreased (both P<0.05). Logistic regression analysis showed that methylation levels at CpG_30.31 and CpG_39.40.41 were independent risk factors affecting the prognosis of sTBI patients (both P<0.05). The ROC curves analysis showed that methylation levels at CpG_30.31 and CpG_39.40.41 could be used as diagnostic indicators to predict the prognosis of sTBI patients (AUC=0.7085, 0.7315, P=0.0014, 0.0004). Methylation levels at CpG_30.31 and CpG_39.40.41 sites of NKCC1 were negatively correlated with mRNA levels of NKCC1 (r=-0.2574, -0.1328, P=0.0138, 0.0325). Conclusion: NKCC1 promoter methylation status can be used as an effective predictor of prognosis in patients with sTBI. |
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