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卒中后抑郁症(post-stroke depression,PSD)是一种卒中神经精神后遗症,是病人功能和治疗结果的重要指标[1]。PSD会干扰卒中的恢复,并与卒中的严重程度、认知障碍和死亡率增加有关[2]。因此,PSD的早期诊断和干预有利于卒中病人的功能恢复。然而,对临床人群中PSD病因机制的研究是有限的。情绪障碍的发生和发展与卒中引起的炎症因子密切相关[3]。研究[4]表明,白细胞介素(IL-10)可以通过降低细胞因子表达和抑制受体激活来限制炎症。IL-10被描述为一种细胞因子合成抑制因子,可以削弱效应器功能,使多个细胞失活,减少内皮细胞损伤,改善血管功能障碍。因此,IL-10在卒中后的炎症反应中发挥抗炎作用[5]。临床研究[6]表明,低IL-10水平与卒中后急性神经系统疾病的发生有关,表明其可能有助于预测PSD。过氧化氢酶(CAT)是一种细胞内抗氧化酶,可将活性氧代谢为毒性较小的分子,并将过氧化氢催化为水和氧气[7]。研究[8]报道,缺血性卒中病人血清CAT水平明显低于对照组,并且血清CAT水平降低可能是PSD发病率的独立预测因素。目前,PSD与IL-10和CAT水平之间的精确关系尚未深入研究,特别是在急性缺血性卒中病人临床随访的PSD发生方面。因此,本研究的主要目的是调查急性缺血性卒中病人入院时IL-10和CAT水平与PSD发生之间的具体关系。
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151例病人的平均年龄为(62.73±9.89)岁,其中89例(58.9%)为男性。入院时有28例(18.5%)患有严重卒中(NIHSS≥7),NIHSS评分中位数为3 (IQR:2~5)。病人的平均住院时间为9.00 d(IQR:7.00~12.00)。出院时BI评分为85.00 (IQR:75.00~100.00),出院时NIHSS评分为3.00 (IQR:1.00~5.00)。39例病人(27.1%)在1个月内出现不良结果(mRS评分≥3)。脑梗死后1个月开始随访,有51例(33.8%)病人被诊断为PSD。与非PSD病人相比,PSD组入院和出院时NIHSS评分较高,脑梗死体积较大,BI评分较低,mRS评分较高(P<0.05)(见表 1),血清CAT、IL-10水平较低(P<0.01)(见表 2)。
分组 n 年龄(x±s)/岁 男[n; 百分率(%)] 体质量(x±s)/kg 身高(x±s)/cm BMI(x±s)/(kg/m2) 受教育年限▲/年 PSD 51 62.10±9.70 31 (60.8) 63.49±10.08 163.65±8.15 23.65±2.91 3.00 (0.00~6.00) 非PSD 100 63.17±9.95 58 (58.0) 63.41±10.63 162.97±7.18 23.82±3.33 3.50 (0.00~6.00) t — 0.61 0.11△ 0.01 0.58 0.38 1.19* P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 分组 血管危险因素[n; 百分率(%)] 高血压 高脂血症 糖尿病 心脏病 抽烟 饮酒 PSD 43 (84.3) 10 (19.6) 19 (37.3) 4 (7.8) 17 (33.3) 12 (23.5) 非PSD 85 (85.0) 17 (17.0) 30 (30.0) 14 (14.0) 30 (30.0) 27 (27.0) t 0.01△ 0.16△ 0.81△ 1.22△ 0.18△ 0.21△ P >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 分组 病变部位[n; 百分率(%)] TOAST亚型[n; 百分率(%)] 脑叶 基底神经节和丘脑 脑干和小脑 多发性梗死 动脉粥样硬化型 心源性栓塞型 腔隙型 其他病因类型 PSD 3 (5.9) 25 (49.0) 11 (21.6) 12 (23.5) 40 (78.4) 2 (3.9) 9 (17.6) 0 (0) 非PSD 8 (8.0) 50 (50.0) 23 (23.0) 19 (19.0) 60 (60.0) 11 (11.0) 28 (28.0) 1 (1.0) t 0.58△ — P >0.05 <0.05 分组 梗死体积▲/cm3 入院时NIHSS▲评分 出院时NIHSS▲评分 住院时间▲/d 出院时BI▲ 1个月时mRS▲ PSD 1.95 (0.86~5.33) 5.00 (2.00~7.00) 4.00 (2.00~6.00) 9.00 (8.00~12.00) 80.00(70.00~90.00) 1.80(1.00~3.00) 非PSD 0.97 (0.38~2.15) 3.00 (2.00~4.00) 3.00 (1.00~4.00) 9.00 (7.00~11.00) 90.00(80.00~100.00) 1.60 (1.00~3.00) t 5.27* 4.91* 5.08* 1.44* 5.42* 5.41* P <0.05 <0.05 <0.05 >0.05 <0.01 <0.01 △示χ2值;*示Z值;▲示IQR值 表 1 缺血性卒中后PSD和非PSD病人的基线特征
分组 Hs-CRP▲/mmol/L) 血小板/(109/L) CAT/(U/L) IL-10/(pg/mL) PSD 5.32 (4.31~7.85) 232.02±69.11 0.60 (0.39~1.17) 1.55 (0.58~3.70) 非PSD 4.84 (4.23~5.91) 210.71±53.77 1.43 (0.65~2.83) 3.68 (2.52~5.08) t 1.43* 1.17 9.43* 12.77* P >0.05 >0.05 <0.01 <0.01 *示Z值;▲示IQR值 表 2 2组血生化指标比较(x±s)
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通过单变量logistic回归分析,IL-10和CAT是PSD的保护性预测因子(P < 0.05)。在调整了包括一般人口学因素、入院和出院时的NIHSS评分、BI评分、1个月后mRS评分、TOAST亚型在内的潜在混杂因素(在单变量logistic回归分析中,P < 0.05)后,IL-10(OR=0.615,95%CI:0.410~0.923)和CAT(OR=0.757,95%CI:0.652~0.914)仍然是PSD的独立预测因子(见表 3)。
特征 模型1 模型2 B SE Waldχ2 OR(95%CI) P B SE Waldχ2 OR(95%CI) P TOAST亚型 0.671 0.260 2.58 0.648 (0.424~0.990) <0.05 — — — — — 入院时NIHSS评分 0.316 0.132 3.09 1.170 (1.043~1.314) <0.05 — — — — — 出院时NIHSS评分 0.198 0.062 3.20 1.192 (1.059~1.342) <0.05 — — — — — 出院时BI 0.576 0.308 3.32 0.944 (0.914~0.976) <0.05 — — — — — 1个月后的mRS 0.316 0.132 3.28 1.823 (1.269~2.617) <0.05 — — — — — CAT/(U/L) 0.107 0.048 2.24 0.706 (0.610~0.912) <0.05 0.283 0.037 2.14 0.757 (0.652~0.914) <0.05 IL-10 /(pg/mL) 0.147 0.050 3.14 0.529 (0.343~0.815) <0.05 0.021 0.023 2.43 0.615 (0.410-0.923) <0.05 注:模型1未调整,模型2调整 表 3 PSD患病情况的多因素logistic分析
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与非PSD病人相比,PSD病人的IL-10水平(1.55 pg/mL,IQR:0.58~3.70 pg/mL vs.3.68 pg/mL,IQR:2.52~5.08 pg/mL;P < 0.01)和CAT水平(0.60 U/L,IQR:0.39~1.17 U/L vs.1.43 U/L,IQR:0.65~2.83 U/L;P < 0.01)显著降低(见表 1)。此外,在双变量相关分析中,PSD病人的IL-10水平(r=0.394,P < 0.01)和CAT水平(r=0.306,P < 0.01)与HAMD评分呈负相关,非PSD病人中未观察到IL-10水平和CAT水平与HAMD评分存在相关性(见图 1)。
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ROC分析结果发现血清IL-10水平的截止点为2.06 pg/mL,预测PSD的AUC为0.739;同时,CAT水平的截止点为1.07 U/L,预测PSD的AUC为0.630(见图 2)。PSD与CAT水平和IL-10水平之间的双变量分析显示,IL-10水平较低(< 2.06 pg/mL)的病人比对应组(≥2.06 pg/mL)更容易发生PSD (P < 0.01)。同样,CAT水平较低(< 1.07 U/L)的病人比对应组(≥1.07 U/L)更容易发生PSD(P < 0.05)(见表 4)。
变量 PSD 非PSD OR(95%CI) P n % n % IL-10/(pg/mL) < 2.06 40 78.4 14 14.0 9.750(2.671~35.534) < 0.01 ≥2.06 11 21.6 86 86.0 1.00 CAT/(U/L) < 2.06 28 54.9 35 35.0 5.052(1.256~20.322) < 0.05 ≥1.07 23 45.1 65 65.0 1.00 表 4 CAT水平和IL-10水平分类与PSD之间关联的双变量分析
白细胞介素10和过氧化氢酶对急性缺血性卒中病人卒中后抑郁的预测价值
Predictive value of interleukin-10 and catalase for post-stroke depression in patients with acute ischemic stroke
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摘要:
目的探讨白细胞介素10(IL-10)和过氧化氢酶(CAT)对急性缺血性卒中病人卒中后抑郁(PSD)的预测价值。 方法151例急性缺血性卒中病人入院后24 h内测定血清IL-10、CAT水平。使用17项汉密尔顿抑郁量表(HAMD-17)来评估抑郁症状;PSD定义为HAMD评分≥8。 结果脑梗死后1个月开始随访,有51例(33.8%) 被诊断为PSD。与非PSD病人相比,PSD组入院和出院时NIHSS评分较高,脑梗死体积较大,BI评分较低,mRS评分较高,血清CAT、IL-10水平较低(P < 0.05)。在调整了潜在混杂因素(在单变量逻辑回归分析中,P < 0.05)后,IL-10(OR=0.615,95%CI:0.410~0.923)和CAT(OR=0.757,95%CI:0.652~0.914)仍然是PSD的独立预测因子。PSD病人的IL-10水平(r=0.394,P < 0.01)和CAT水平(r=0.306,P < 0.01)与HAMD评分呈负相关。ROC分析显示,血清IL-10水平的截止点为2.06 pg/mL,预测PSD的AUC为0.739。同时,CAT水平的截止点为1.07 U/L,预测PSD的AUC为0.630。IL-10水平较低(< 2.06 pg/mL)的病人比对应组(≥2.06 pg/mL)更容易发生PSD (OR=9.750,95%CI=2.671~35.534,P < 0.01)。同样,CAT水平较低(< 1.07 U/L)的病人比对应组(≥1.07 U/L)更容易发生PSD (OR=5.052,95%CI=1.256~20.322,P < 0.05)。 结论血清IL-10、CAT可用作急性缺血性卒中病人PSD的独立保护性预测因子。IL-10、CAT水平低的病人在卒中后1个月更有可能发生PSD。 Abstract:ObjectiveTo investigate the predictive value of interleukin-10 (IL-10) and catalase (CAT) in post-stroke depression (PSD) in patients with acute ischemic stroke. MethodsSerum IL-10 and CAT levels in 151 patients with acute ischemic stroke within 24 h of hospital admission were measured.Depressive symptoms were assessed using the 17-item Hamilton depression scale (HAMD-17), and PSD was defined as a HAMD score ≥8. ResultsAt 1-month follow-up after stroke, 51 (33.8%) patients were diagnosed with PSD.Compared with non-PSD patients, the PSD group had higher NIHSS scores at admission and discharge, larger cerebral infarction volume, lower BI score, higher mRS score, and lower serum CAT and IL-10 levels (P < 0.05).After adjusting for potential confounders (P < 0.05 in univariate logistic regression analysis), IL-10 (OR=0.615, 95%CI: 0.410-0.923) and CAT (OR=0.757, 95%CI: 0.652-0.914) were independent predictors of PSD.IL-10 levels (r=0.394, P < 0.01) and CAT levels (r=0.306, P < 0.01) were negatively correlated with HAMD scores in PSD patients.ROC analysis showed that the cutoff point for serum IL-10 levels was 2.06 pg/mL, and the AUC for predicting PSD was 0.739.Meanwhile, the cutoff point for the CAT level was 1.07 U/L, and the AUC for predicting PSD was 0.630.Patients with lower IL-10 levels (< 2.06 pg/mL) were more likely to develop PSD than their counterparts (≥2.06 pg/mL) (OR=9.750, 95%CI=2.671-35.534, P < 0.01).Meanwhile, patients with lower CAT levels (< 1.07 U/L) were more likely to develop PSD than their counterparts (≥1.07 U/L) (OR=5.052, 95%CI=1.256-20.322, P < 0.05). ConclusionsSerum IL-10 and CAT can be used as independent protective predictors of PSD in patients with acute ischemic stroke.Patients with low levels of IL-10 and CAT are more likely to develop PSD 1 month after stroke. -
Key words:
- acute ischemic stroke /
- interleukin 10 /
- catalase /
- post-stroke depression
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表 1 缺血性卒中后PSD和非PSD病人的基线特征
分组 n 年龄(x±s)/岁 男[n; 百分率(%)] 体质量(x±s)/kg 身高(x±s)/cm BMI(x±s)/(kg/m2) 受教育年限▲/年 PSD 51 62.10±9.70 31 (60.8) 63.49±10.08 163.65±8.15 23.65±2.91 3.00 (0.00~6.00) 非PSD 100 63.17±9.95 58 (58.0) 63.41±10.63 162.97±7.18 23.82±3.33 3.50 (0.00~6.00) t — 0.61 0.11△ 0.01 0.58 0.38 1.19* P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 分组 血管危险因素[n; 百分率(%)] 高血压 高脂血症 糖尿病 心脏病 抽烟 饮酒 PSD 43 (84.3) 10 (19.6) 19 (37.3) 4 (7.8) 17 (33.3) 12 (23.5) 非PSD 85 (85.0) 17 (17.0) 30 (30.0) 14 (14.0) 30 (30.0) 27 (27.0) t 0.01△ 0.16△ 0.81△ 1.22△ 0.18△ 0.21△ P >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 分组 病变部位[n; 百分率(%)] TOAST亚型[n; 百分率(%)] 脑叶 基底神经节和丘脑 脑干和小脑 多发性梗死 动脉粥样硬化型 心源性栓塞型 腔隙型 其他病因类型 PSD 3 (5.9) 25 (49.0) 11 (21.6) 12 (23.5) 40 (78.4) 2 (3.9) 9 (17.6) 0 (0) 非PSD 8 (8.0) 50 (50.0) 23 (23.0) 19 (19.0) 60 (60.0) 11 (11.0) 28 (28.0) 1 (1.0) t 0.58△ — P >0.05 <0.05 分组 梗死体积▲/cm3 入院时NIHSS▲评分 出院时NIHSS▲评分 住院时间▲/d 出院时BI▲ 1个月时mRS▲ PSD 1.95 (0.86~5.33) 5.00 (2.00~7.00) 4.00 (2.00~6.00) 9.00 (8.00~12.00) 80.00(70.00~90.00) 1.80(1.00~3.00) 非PSD 0.97 (0.38~2.15) 3.00 (2.00~4.00) 3.00 (1.00~4.00) 9.00 (7.00~11.00) 90.00(80.00~100.00) 1.60 (1.00~3.00) t 5.27* 4.91* 5.08* 1.44* 5.42* 5.41* P <0.05 <0.05 <0.05 >0.05 <0.01 <0.01 △示χ2值;*示Z值;▲示IQR值 表 2 2组血生化指标比较(x±s)
分组 Hs-CRP▲/mmol/L) 血小板/(109/L) CAT/(U/L) IL-10/(pg/mL) PSD 5.32 (4.31~7.85) 232.02±69.11 0.60 (0.39~1.17) 1.55 (0.58~3.70) 非PSD 4.84 (4.23~5.91) 210.71±53.77 1.43 (0.65~2.83) 3.68 (2.52~5.08) t 1.43* 1.17 9.43* 12.77* P >0.05 >0.05 <0.01 <0.01 *示Z值;▲示IQR值 表 3 PSD患病情况的多因素logistic分析
特征 模型1 模型2 B SE Waldχ2 OR(95%CI) P B SE Waldχ2 OR(95%CI) P TOAST亚型 0.671 0.260 2.58 0.648 (0.424~0.990) <0.05 — — — — — 入院时NIHSS评分 0.316 0.132 3.09 1.170 (1.043~1.314) <0.05 — — — — — 出院时NIHSS评分 0.198 0.062 3.20 1.192 (1.059~1.342) <0.05 — — — — — 出院时BI 0.576 0.308 3.32 0.944 (0.914~0.976) <0.05 — — — — — 1个月后的mRS 0.316 0.132 3.28 1.823 (1.269~2.617) <0.05 — — — — — CAT/(U/L) 0.107 0.048 2.24 0.706 (0.610~0.912) <0.05 0.283 0.037 2.14 0.757 (0.652~0.914) <0.05 IL-10 /(pg/mL) 0.147 0.050 3.14 0.529 (0.343~0.815) <0.05 0.021 0.023 2.43 0.615 (0.410-0.923) <0.05 注:模型1未调整,模型2调整 表 4 CAT水平和IL-10水平分类与PSD之间关联的双变量分析
变量 PSD 非PSD OR(95%CI) P n % n % IL-10/(pg/mL) < 2.06 40 78.4 14 14.0 9.750(2.671~35.534) < 0.01 ≥2.06 11 21.6 86 86.0 1.00 CAT/(U/L) < 2.06 28 54.9 35 35.0 5.052(1.256~20.322) < 0.05 ≥1.07 23 45.1 65 65.0 1.00 -
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