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目的 观察重度恶性大脑中动脉梗死（malignant middle cerebral artery infarction，MMCAI）患者早期血清MMP组织抑制剂（tissue inhibitor of matrix metalloproteinase，TIMP）3水平变化，确定其对患者30 d死亡的预测价值。 方法 前瞻性纳入南京医科大学附属明基医院神经内科2019年2月—2022年1月收治的MMCAI患者，根据30 d结局分为存活组和死亡组。采用免疫分析法检测患者入院第1天、第4天和第8天时血清TIMP-1、TIMP-2、TIMP-3、TIMP-4水平。ROC曲线分析TIMP对MMCAI患者30 d死亡的预测价值，多因素logistic回归分析患者30 d死亡的危险因素。 结果 共入组MMCAI患者68例，其中30 d内全因死亡34例。与存活组相比，死亡组入院第1天血清TIMP-1水平[100.86（77.85～137.33）ng/mL vs. 70.15（61.70～82.83）ng/mL，P=0.001]，以及第1天[309.86（210.03～614.72）ng/mL vs. 174.54（120.90～347.75）ng/mL，P＜0.001]、第4天[288.32（167.45～371.38）ng/mL vs. 172.42（99.06～232.47）ng/mL，P=0.003]和第8天[297.91（238.98～353.83）ng/mL vs. 118.26（81.59～190.70）ng/mL，P＜0.001]的血清TIMP-3水平较存活组均显著升高。ROC曲线分析显示，入院第1天、第4天和第8天血清TIMP-3水平预测MMCAI患者30 d死亡的AUC分别为0.751（95%CI 0.636～0.866，P＜0.001，截断值为179.33 ng/mL）、0.748（95%CI 0.606～0.889，P＜0.001，截断值为333.41 ng/mL）、0.840（95%CI 0.726～0.955，P＜0.001，截断值为266.56 ng/mL）。多元logistic回归分析表明，在校正血小板计数、GCS评分和乳酸水平后，入院第1天血清TIMP-3水平升高仍是影响MMCAI患者30 d死亡的独立危险因素（OR 1.006，95%CI 1.002～1.011，P=0.008）。生存分析显示，入院第1天血清TIMP-3水平＞257.93 ng/mL的患者30 d死亡率更高（P＜0.001）。 结论 血清TIMP-3水平变化是MMCAI患者30 d死亡的危险因素，入院第1天血清TIMP-3水平可作为预测MMCAI患者死亡的生物标志物。 Abstract: Objective By observing the changes of serum tissue inhibitor of matrix metalloproteinase (TIMP) -3 levels in patients with severe malignant middle cerebral artery infarction (MMCAI), and to determine its predictive value for hospital death in patients with MMCAI. Methods Sixty-eight patients with MMCAI admitted to Mingji Hospital Affiliated to Nanjing Medical University from February 2019 to January 2022 were selected, and the patients divided into survival group and death group according to 30-day in-hospital outcomes. Serum TIMP-1, TIMP-2, TIMP-3, and TIMP-4 levels on day 1, day 4 and day 8 of admission were detected by immunoassay. ROC was established to analyze the predictive value of 30-day death in patients with MMCAI, and multivariate logistic regression was used to analyze the risk factors of 30-day death in patients with MMCAI. Results Among 68 patients with MMCAI, 34 died within 30 days. Compared with the survival group, the serum TIMP-1 level in the death group was significantly increased on day 1 of admission [100.86 (77.85-137.33) ng/mL vs. 70.15 (61.70-82.83) ng/mL, P=0.001], and the serum TIMP-3 level on day 1 [309.86 (210.03-614.72) ng/mL vs. 174.54 (120.90-347.75) ng/mL, P257.93 ng/mL on day 1 of admission had higher 30-day mortality (P |
