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肌萎缩侧索硬化(amyotrophic lateral sclerosis, ALS)是一类累及上、下运动神经元的神经退行性疾病,病理特征是脊髓、脑干和运动皮层运动神经元的丢失[1]。迄今为止ALS发生机制尚不清楚,越来越多的证据表明神经系统炎症在ALS发病中起重要作用[2]。文献[3]显示,ALS中的神经系统炎症特征在于淋巴细胞和巨噬细胞的浸润,小胶质细胞和反应性星形胶质细胞的活化以及补体的参与。趋化因子可由小胶质细胞、神经元、活化的星形胶质细胞和单核巨噬细胞等产生,在免疫细胞的募集和激活上起着重要的调控作用[4]。趋化因子配体2(chemokine ligand-2,CCL2),能够趋化多种免疫细胞到达组织损伤或感染的部位参与炎症反应。CCL2引起Tau蛋白的聚集,引起神经系统炎症加重阿尔茨海默病人的认知功能障碍[5]。本研究收集32例ALS病人和20例肌肉病病人的血浆,ELISA法分析CCL2和白细胞介素6(interleukin 6, IL-6)水平, 利用简易智能量表(mini-mental state examination,MMSE)和及韦氏记忆量表(Wechsler intelligence scale,WMS)评估病人的认知功能情况,明确CCL2和IL-6水平变化对ALS病人认知功能的影响。
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2组年龄、性别和教育程度差异均无统计学意义(P>0.05)(见表 1)。
分组 n 男 女 年龄/岁 教育程度/年 对照组 32 10 10 58.8±0.66 8.63±0.29 观察组 20 15 17 59.2±0.64 9.1±0.61 t — 0.05* 2.15 3.23 P — >0.05 >0.05 >0.05 *示χ2值 表 1 2组病人一般资料比较(x±s)
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观察组CCL2和IL-6水平分别为(29.55±2.65)pg/mL和(9.59±0.87)pg/mL,对照组分别为(14.5±0.49) pg/mL和(3.86±0.43)pg/mL,观察组CCL2和IL-6水平均明显高于对照组(t=4.44, P < 0.01;t=4.98, P < 0.01)。
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观察组病人MMSE评分和WMS评分均高于对照组(P < 0.05~P < 0.01),观察组记忆优于对照组(Zc=-2.64,P < 0.01)(见表 2)。
分组 MMSE评分 WMS评分 记忆 记忆商 长时记忆 短时记忆 瞬时记忆 障碍 边界 正常 对照组 26.67±0.37 86.09±2.54 25.7±0.33 52.4±1.84 8.81±0.21 0 1 19 观察组 29.4±0.17 95.35±1.96 27.9±0.65 58.2±1.76 9.35±1.02 5 7 20 t 36.09 13.90 14.05 11.24 2.34 2.64 P < 0.01 < 0.01 < 0.01 < 0.01 < 0.05 < 0.01 *示Zc值 表 2 2组病人MMSE和WMS评分比较(x±s;分)
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观察组血清CCL2和IL-6与认知功能相关性分析显示,CCL2水平与MMSE评分和WMS评分呈负相关关系(P < 0.05),而IL-6水平与MMSE评分和WMS评分无明显相关关系(P>0.05)。对照组CCL2和IL-6与认知功能评分均无明显相关关系(P>0.05)(见表 3)。
项目 MMSE评分 WMS评分 r P r P 观察组CCL2 -0.330 < 0.05 -0.377 < 0.05 观察组IL-6 -0.137 >0.05 -0.126 >0.05 对照组CCL2 -0.147 >0.05 0.155 >0.05 对照组IL-6 0.123 >0.05 0.105 >0.05 表 3 血浆CCL2和IL-6与认知功能评分的相关性分析
肌萎缩侧索硬化病人CCL2和IL-6的表达水平与认知功能的相关性研究
Study on the correlation of the levels of CCL2 and IL-6 with cognitive function in amyotrophic lateral sclerosis patients
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摘要:
目的检测肌萎缩侧索硬化病人的外周血趋化因子配体2(chemokine ligand-2,CCL2)和白细胞介素6(interleukin 6,IL-6)的表达水平及与认知功能评分的相关性。 方法选择肌萎缩侧索硬化病人32例(观察组)和肌肉病病人(对照组)20例,ELISA法检测血浆CCL2和IL-6的水平,利用简易智能量表(Mini-mental State Examination,MMSE)和韦氏记忆量表(Wechsler Intelligence Scale,WMS)评估病人的认知功能情况。 结果2组病人的年龄、性别和教育程度差异均无统计学意义(P>0.05)。ELISA检测结果显示,观察组CCL2和IL-6水平均明显高于对照组(P < 0.01)。观察组MMSE评分明显低于对照组(P < 0.01);观察组WMS中记忆商、长时记忆、短时记忆和瞬时记忆得分均低于对照组(P < 0.05~P < 0.01)。观察组CCL2与MMSE评分和WMS评分均呈负相关关系(P < 0.05)。 结论肌萎缩侧索硬化病人血浆CCL2和IL-6较肌肉病病人增加,存在认知功能下降;外周血CCL2水平与认知功能障碍有关。 Abstract:ObjectiveTo detect the levels of chemokine ligand-2(CCL2) and interleukin 6(IL-6) in peripheral blood in amyotrophic lateral sclerosis(ALS) patients, and analyze the correlation of the levels of CCL2 and IL-6 with cognitive function. MethodsThirty-two ALS patients and 20 myopathy patients were divided into the observation group and control group, respectively.The plasma levels of CCL2 and IL-6 in two groups were detected using ELISA, and the cognitive function in two groups were evaluated using Mini-mental State Examination(MMSE) and Wechsler Intelligence Scale(WMS). ResultsThe differences of the age, gender and education level between two groups were not statistically significant(P>0.05).The results of ELISA showed that the levels of CCL2 and IL-6 in observation group were higher than those in control group(P < 0.01).The MMSE score in observation group was lower than that in control group(P < 0.01).The scores of the memory quotient, long-term memory, short-term and transient memory in observation group were lower than those in control group(P < 0.05 to P < 0.01).The level of CCL2 was negatively correlated with the MMSE score and WMS score(P < 0.05). ConclusionsCompared with the myopathy patients, the plasma levels of CCL2 and IL-6 are upregulated, and the cognitive function decrease in ALS patients.The level of CCL2 in peripheral blood is negatively correlated to the cognitive function of patients. -
表 1 2组病人一般资料比较(x±s)
分组 n 男 女 年龄/岁 教育程度/年 对照组 32 10 10 58.8±0.66 8.63±0.29 观察组 20 15 17 59.2±0.64 9.1±0.61 t — 0.05* 2.15 3.23 P — >0.05 >0.05 >0.05 *示χ2值 表 2 2组病人MMSE和WMS评分比较(x±s;分)
分组 MMSE评分 WMS评分 记忆 记忆商 长时记忆 短时记忆 瞬时记忆 障碍 边界 正常 对照组 26.67±0.37 86.09±2.54 25.7±0.33 52.4±1.84 8.81±0.21 0 1 19 观察组 29.4±0.17 95.35±1.96 27.9±0.65 58.2±1.76 9.35±1.02 5 7 20 t 36.09 13.90 14.05 11.24 2.34 2.64 P < 0.01 < 0.01 < 0.01 < 0.01 < 0.05 < 0.01 *示Zc值 表 3 血浆CCL2和IL-6与认知功能评分的相关性分析
项目 MMSE评分 WMS评分 r P r P 观察组CCL2 -0.330 < 0.05 -0.377 < 0.05 观察组IL-6 -0.137 >0.05 -0.126 >0.05 对照组CCL2 -0.147 >0.05 0.155 >0.05 对照组IL-6 0.123 >0.05 0.105 >0.05 -
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