Value of serum absent in melanoma 2 expression level in predicting occurrence of early neurological deterioration after alteplase intravenous thrombolysis in patients with acute cerebral infarction
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摘要:目的
探讨急性脑梗死(ACI)患者血清黑素瘤缺乏因子2(AIM2)表达水平与病情严重程度的相关性, 并评估AIM2预测ACI患者阿替普酶静脉溶栓治疗后发生早期神经功能恶化(END)的价值。
方法选取150例ACI患者为ACI组，另选取30例健康体检者为对照组。ACI患者入院时根据美国国立卫生研究院卒中量表(NIHSS)评分分为轻度组、中度组和重度组，根据静脉溶栓治疗后END情况分为END组和非END组。收集ACI患者的临床资料; 采用酶联免疫吸附试验(ELISA)测定血清AIM2表达水平; 采用Logistic回归模型分析ACI患者静脉溶栓治疗后发生END的影响因素; 绘制受试者工作特征(ROC)曲线分析血清AIM2表达水平预测ACI患者静脉溶栓治疗后发生END的临床效能。
结果ACI组、对照组血清AIM2表达水平分别为(58.29±5.97)、(36.81±3.03) ng/mL, 差异有统计学意义(t=43.23, P < 0.05)。轻度组、中度组和重度组血清AIM2表达水平逐渐升高，两两比较差异均有统计学意义(P < 0.01)。ACI患者血清AIM2表达水平与NIHSS评分呈正相关(r=0.941, P < 0.01)。END组NIHSS评分、入院到溶栓时间、低密度脂蛋白胆固醇(LDL-C)、C反应蛋白、AIM2水平高于或长于非END组，差异有统计学意义(P < 0.05)。多因素Logistic回归分析结果显示, NIHSS评分(OR=3.871, P < 0.001)、入院到溶栓时间(OR=2.885, P=0.002)、LDL-C(OR=3.118, P < 0.001)和AIM2(OR=3.761, P < 0.001)均为ACI患者静脉溶栓术后发生END的影响因素。ROC曲线结果显示, ACI患者入院时血清AIM2表达水平预测静脉溶栓术后发生END的曲线下面积(AUC)为0.911; 当AIM2截断值为66.56 ng/mL时，诊断敏感度和特异度分别为91.23%和90.15%。
结论ACI患者血清AIM2表达水平显著升高; AIM2表达水平预测ACI患者静脉溶栓治疗后发生END具有一定优势。
Abstract:ObjectiveTo investigate the correlation between the expression level of absent in melanoma 2 (AIM2) in serum and the severity of acute cerebral infarction (ACI), and to evaluate the value of AIM2 in predicting early neurological deterioration (END) after intravenous thrombolysis with alteplase in ACI patients.
MethodsA total of 150 ACI patients were enrolled in ACI group, and another 30 healthy individuals physical examination were selected as control group. ACI patients were further divided into mild, moderate and severe groups according to the National Institutes of Health Stroke Scale (NIHSS) score at admission, and they were also divided into END and non-END groups based on the occurrence of END after intravenous thrombolysis. Clinical materials of ACI patients were collected; the expression level of serum AIM2 was measured by enzyme-linked immunosorbent assay (ELISA); the Logistic regression analysis was performed to identify the factors influencing END after intravenous thrombolysis in ACI patients; the receiver operating characteristic (ROC) curve was plotted to analyze the clinical performance of serum AIM2 expression level in predicting END after intravenous thrombolysis in ACI patients.
ResultsThe serum AIM2 expression level in the ACI group and the control group was (58.29±5.97) and (36.81±3.03) ng/mL respectively, with a significant between-group difference (t=43.23, P < 0.05). The serum AIM2 expression level gradually increased in the mild, moderate and severe groups, with significant differences between each pair of groups (P < 0.01). The serum AIM2 expression level in ACI patients was positively correlated with the NIHSS score (r=0.941, P < 0.01). The NIHSS score, time from admission to thrombolysis, low-density lipoprotein cholesterol (LDL-C), C-reactive protein, and AIM2 level in the END group were significantly higher or longer than those in the non-END group (P < 0.05). The results of multivariate Logistic regression analysis showed that NIHSS score (OR=3.871, P < 0.001), time from admission to thrombolysis (OR=2.885, P=0.002), LDL-C (OR=3.118, P < 0.001) and AIM2 (OR=3.761, P < 0.001) were influencing factors for END after intravenous thrombolysis in ACI patients. ROC curve showed that the area under the curve (AUC) for predicting END after intravenous thrombolysis based on the serum AIM2 expression level at admission in ACI patients was 0.911; when the cut-off value of AIM2 was 66.56 ng/mL, the diagnostic sensitivity and specificity were 91.23% and 90.15%, respectively.
ConclusionThe expression level of serum AIM2 is significantly increased in ACI patients, and AIM2 expression level has certain advantages in predicting END after intravenous thrombolysis in ACI patients.
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表 1 ACI患者血清AIM2表达水平与病情严重程度的关系(x±s)
组别 n AIM2/(ng/mL) NIHSS评分/分 轻度组 11 47.69±4.55 4.43±0.15 中度组 86 53.29±5.42** 13.45±2.62** 重度组 53 65.87±6.16**## 20.06±3.11**## F 43.22 35.69 P < 0.001 < 0.001 ACI: 急性脑梗死; AIM2: 黑素瘤缺乏因子2;
NIHSS: 美国国立卫生研究院卒中量表。
与轻度组比较, * * P < 0.01; 与中度组比较, ##P < 0.01。
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表 2 非END组与END组基线资料比较(x±s)[n(%)]
基线资料 分类 非END组(n=98) END组(n=52) t/χ2 P 性别(男) 55(56.12) 25(48.08) 0.884 0.347 年龄/岁 55.78±4.69 54.96±4.18 1.057 0.292 NIHSS评分/分 14.23±4.30 19.67±3.28 7.971 < 0.001 病程/h 19.93±2.88 20.11±2.45 0.383 0.702 合并疾病 高血压、糖尿病及高脂血症 26(26.53) 19(36.54) 1.620 0.203 无 72(73.47) 33(63.46) 吸烟及饮酒史 有 24(24.49) 16(30.77) 0.685 0.408 无 74(75.51) 36(69.23) 梗死部位 基底节 65(66.33) 34(65.38) 0.013 0.908 其他 33(33.67) 18(34.62) 梗死类型 单发脑梗死 70(71.43) 41(78.85) 0.972 0.324 多发脑梗死 28(28.57) 11(21.15) 入院到溶栓时间/min 40.34±5.55 53.23±4.38 14.513 < 0.001 收缩压/mmHg 143.23±18.98 144.05±19.55 0.249 0.804 舒张压/mmHg 95.55±10.48 95.67±9.29 0.069 0.945 血糖/(mmol/L) 6.08±1.48 5.94±1.45 0.555 0.580 ALT/(U/L) 26.45±3.44 27.01±3.98 0.898 0.371 AST/(U/L) 30.66±5.21 29.06±3.99 1.933 0.055 Cr/(μmol/L) 86.77±8.49 87.05±7.05 0.203 0.839 TG/(mmol/L) 1.51±0.22 1.57±0.31 1.373 0.172 TC/(mmol/L) 3.48±0.78 3.43±0.62 0.400 0.690 LDL-C/(mmol/L) 2.33±0.38 4.22±0.49 26.157 < 0.001 同型半胱氨酸/(μmol/L) 45.33±4.01 46.08±4.61 1.034 0.303 D-二聚体/(mg/L) 0.67±0.11 0.68±0.13 0.497 0.620 C反应蛋白/(mg/L) 18.68±4.91 34.34±5.66 17.619 < 0.0012 AIM2/(ng/mL) 51.48±5.45 64.33±6.34 12.976 < 0.001 END: 早期神经功能恶化; NIHSS: 美国国立卫生研究院卒中量表; ALT: 谷氨酸-丙酮酸转氨酶; AST: 天门冬氨酸转氨酶;
Cr: 肌酐; TG: 甘油三酯; TC: 总胆固醇; LDL-C: 低密度脂蛋白胆固醇; AIM2: 黑素瘤缺乏因子2。1 mmHg=0.133 kPa。
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表 3 ACI患者静脉溶栓术后发生END的影响因素分析
因素 B SE Wald χ2 OR(95%CI) P 常数项 0.938 0.332 7.982 2.554(—) 0.024 NIHSS评分 1.353 0.664 4.155 3.871(1.554~7.225) < 0.001 入院到溶栓时间 1.059 0.483 4.812 2.885(1.468~7.329) 0.002 LDL-C 1.137 0.571 3.966 3.118(1.592~6.005) < 0.001 AIM2 1.324 0.585 5.127 3.761(1.736~7.031) < 0.001
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