不同程度肺气肿表型慢阻肺患者血清同型半胱氨酸、趋化因子配体2水平与认知功能障碍的关系
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摘要
目的观察不同程度肺气肿表型慢性阻塞性肺疾病(简称慢阻肺)患者血清同型半胱氨酸(HCY)、趋化因子配体2(CCL2)水平与认知功能障碍的关系。方法纳入2016年1月至2017年3月依据肺气肿表型分型确定的慢阻肺患者共62例,其中肺气肿1~2级37例(1~2级亚组),3~4级25例(3~4级亚组),同期健康体检者30例作为对照(体检组)。完善蒙特利尔认知评估(MoCA)量表调查及血清HCY、CCL2检测。统计分析不同程度肺气肿表型慢阻肺患者血清HCY、CCL2水平与认知功能障碍的关系。结果肺气肿慢阻肺患者中,3~4级亚组与1~2级亚组比较,PaO_2降低、PaCO_2升高,血浆HCY、CCL2水平升高,差异有统计学意义(均P<0.05)。肺气肿慢阻肺组MoCA评分总分及各亚项评分(除1~2级亚组视空间执行能力评分外)均较体检组低;肺气肿慢阻肺患者中3~4级亚组MoCA评分均低于1~2级亚组,差异有统计学意义(均P<0.05)。HCY和CLL2水平与MoCA评分总分及其亚项评分均呈负相关(P<0.01),HCY与CLL2呈正相关(P<0.01)。对肺气肿慢阻肺患者血清HCY、CLL2水平与认知障碍进行受试者工作特征(ROC)曲线分析,血清HCY、CLL2诊断认知障碍的ROC曲线下面积分别为0.79、0.97。结论不同程度肺气肿表型患者血清HCY、CCL2水平存在不同程度升高,肺气肿程度、HCY、CCL2水平与认知功能障碍关系紧密。
Objective To observe the relationship of serum levels of homocysteine(HCY) and chemokine C-C motif ligand 2(CCL2) with cognitive impairment in COPD patients with different degrees of emphysema. Methods Sixty-two COPD patients identified according to emphysema phenotype classification and admitted from January 2016 to March 2017 were recruited in the study. There were 37 cases in emphysema 1-2 grade and 25 cases in emphysema 3-4 grade.Simultaneous 30 healthy subjects undergoing physical examination were recruited as control. Montreal cognitive assessment(MoCA) scale investigation and serum HCY and CCL2 test were completed. Relationship analysis was conducted on serum HCY, CCL2 levels with cognitive impairment in the COPD patients with different degrees of emphysema. Results Compared with the 1-2 grade subgroup, the PaO_2 was lower, PaCO_2 was higher, the plasma HCY and CCL2 levels increased in the 3-4 grade subgroup with significant differences(all P<0.05). MoCA total score and subscores were relatively low in the COPD group with emphysema than the control group(except visuospatial ability scores in the 1-2 grade subgroup). MoCA scores were statistically lower in the 3-4 grade subgroup than those in the 1-2 grade subgroup(all P<0.05). Correlation analysis showed that HCY and CLL2 levels were negatively correlated with Mo CA scores and subscores(P<0.01), and HCY and CLL2 were positively correlated(both P<0.01). The area under the receiver operating characteristic curve of HCY and CLL2 for evaluating cognitive impairment was 0.79 and 0.97,respectively. Conclusion In patients with different degrees of emphysema phenotype, serum HCY and CCL2 levels are increased in different degree, and the degree of emphysema is closely related with cognitive dysfunction.
Objective To observe the relationship of serum levels of homocysteine(HCY) and chemokine C-C motif ligand 2(CCL2) with cognitive impairment in COPD patients with different degrees of emphysema. Methods Sixty-two COPD patients identified according to emphysema phenotype classification and admitted from January 2016 to March 2017 were recruited in the study. There were 37 cases in emphysema 1-2 grade and 25 cases in emphysema 3-4 grade.Simultaneous 30 healthy subjects undergoing physical examination were recruited as control. Montreal cognitive assessment(MoCA) scale investigation and serum HCY and CCL2 test were completed. Relationship analysis was conducted on serum HCY, CCL2 levels with cognitive impairment in the COPD patients with different degrees of emphysema. Results Compared with the 1-2 grade subgroup, the PaO_2 was lower, PaCO_2 was higher, the plasma HCY and CCL2 levels increased in the 3-4 grade subgroup with significant differences(all P<0.05). MoCA total score and subscores were relatively low in the COPD group with emphysema than the control group(except visuospatial ability scores in the 1-2 grade subgroup). MoCA scores were statistically lower in the 3-4 grade subgroup than those in the 1-2 grade subgroup(all P<0.05). Correlation analysis showed that HCY and CLL2 levels were negatively correlated with Mo CA scores and subscores(P<0.01), and HCY and CLL2 were positively correlated(both P<0.01). The area under the receiver operating characteristic curve of HCY and CLL2 for evaluating cognitive impairment was 0.79 and 0.97,respectively. Conclusion In patients with different degrees of emphysema phenotype, serum HCY and CCL2 levels are increased in different degree, and the degree of emphysema is closely related with cognitive dysfunction.
引文
[1]Han MK,Agusti A,Calverley PM,et al.Chronic obstructive pulmonary disease phenotypes:the future of COPD.Am J Respir Crit Care Med,2010,182(5):598-604.
2 Dodd JW,Getov SV,Jones PW.Cognitive function in COPD.Eur Respir J,2010,35(4):913-922.
3董芳,杜怡峰.腔隙性脑梗死患者认知障碍与高同型半胱氨酸血症、梗死灶数目及体积的相关性.山东大学学报(医学版),2016,54(10):46-49,54.
4 Cervellati C,Romani A,Seripa D,et al.Oxidative balance,homocysteine,and uric acid levels in older patients with late onset Alzheimer's disease or vascular dementia.J Neurol Sci,2014,337(1-2):156-161.
5Sokolova A,Hill MD,Rahimi F,et al.Monocyte chemoattractant protein-1 plays a dominant role in the chronic inflammation observed in Alzheimer's disease.Brain Pathol,2009,19(3):392-398.
6Yamamoto M,Horiba M,Buescher JL,et al.Overexpression of monocyte chemotactic protein-1/CCL2 in beta-amyloid precursor protein transgenic mice show accelerated diffuse beta-amyloid deposition.Am J Pathol,2005,166(5):1475-1485.
7 El KJ,Luster AD.Mechanisms of microglia accumulation in Alzheimer's disease:therapeutic implications.Trends Pharmacol Sci,2008,29(12):626-632.
8Pistolesi M,Camiciottoli G,Paoletti M,et al.Identification of a predominant COPD phenotype in clinical practice.Respir Med,2008,102(3):367-376.
9 Fujimoto K,Kitaguchi Y,Kubo K,et al.Clinical analysis of chronic obstructive pulmonary disease phenotypes classified using highresolution computed tomography.Respirology,2006,11(6):731-740.
10Kitaguchi Y,Fujimoto K,Kubo K,et al.Characteristics of COPD phenotypes classified according to the findings of HRCT.Respir Med,2006,100(10):1742-1752.
11 李然,白澎,孙永昌,等.慢性阻塞性肺疾病肺气肿表型的临床与病理生理特征分析.中华结核和呼吸杂志,2011,34(11):857-858.
12Ley-Zaporozhan J,van Beek EJ.Imaging phenotypes of chronic obstructive pulmonary disease.J Magn Reson Imaging,2010,32(6):1340-1352.
13 凌芳,李瑛,胡成平.慢性阻塞性肺疾病肺气肿表型CT GOD评分与肺功能及其预后的相关性研究.中国实用内科杂志,2014,34 (S1):37-38.
14Barbosa EM,Song G,Tustison N,et al.Computational analysis of thoracic multidetector row HRCT for segmentation and quantification of small airway air trapping and emphysema in obstructive pulmonary disease.Acad Radiol,2011,18(10):1258-1269.
15 张伟宏,蔡柏蔷,王京兰,等.肺气肿的CT肺功能成像:CT技术与肺功能检查的对照研究.中华结核和呼吸杂志,2002,25(3):150-153.
16张敏,张盼盼,韩晓庆,等.不同程度慢性间歇低氧对大鼠齿状回Nogo-A和Ng R表达的影响.中华老年心脑血管病杂志,2015,17(5):522-525.
17 Mathur R,Cox IJ,Oatridge A,et al.Cerebral bioenergetics in stable chronic obstructive pulmonary disease.Am J Respir Crit Care Med,1999,160(6):1994-1999.
18Kirkil G,Tug T,Ozel E,et al.The evaluation of cognitive functions with P300 test for chronic obstructive pulmonary disease patients in attack and stable period.Clin Neurol Neurosurg,2007,109(7):553-560.
19 李力仙,江涛.单核/巨噬细胞及其趋化因子与脑缺血再灌注损伤.国外医学(脑血管疾病分册),2000,8(2):89-91.
20谭曦舒,李立群,胡玲玲,等.COPD患者血清MCP-1、SAA水平与认知功能的相关性研究.四川大学学报(医学版),2016,47(6):957-959.
21 Li JG,Chu J,Barrero C,et al.Homocysteine exacerbatesβ-amyloid pathology,tau pathology,and cognitive deficit in a mouse model of Alzheimer disease with plaques and tangles.Ann Neurol,2014,75(6):851-863.
22桂心,谢小红,张仁荣,等.高同型半胱氨酸血症与脑梗死合并慢性阻塞性肺疾病患者认知障碍的相关性及药物干预研究.中国生化药物杂志,2015,35(4):116-118.
2 Dodd JW,Getov SV,Jones PW.Cognitive function in COPD.Eur Respir J,2010,35(4):913-922.
3董芳,杜怡峰.腔隙性脑梗死患者认知障碍与高同型半胱氨酸血症、梗死灶数目及体积的相关性.山东大学学报(医学版),2016,54(10):46-49,54.
4 Cervellati C,Romani A,Seripa D,et al.Oxidative balance,homocysteine,and uric acid levels in older patients with late onset Alzheimer's disease or vascular dementia.J Neurol Sci,2014,337(1-2):156-161.
5Sokolova A,Hill MD,Rahimi F,et al.Monocyte chemoattractant protein-1 plays a dominant role in the chronic inflammation observed in Alzheimer's disease.Brain Pathol,2009,19(3):392-398.
6Yamamoto M,Horiba M,Buescher JL,et al.Overexpression of monocyte chemotactic protein-1/CCL2 in beta-amyloid precursor protein transgenic mice show accelerated diffuse beta-amyloid deposition.Am J Pathol,2005,166(5):1475-1485.
7 El KJ,Luster AD.Mechanisms of microglia accumulation in Alzheimer's disease:therapeutic implications.Trends Pharmacol Sci,2008,29(12):626-632.
8Pistolesi M,Camiciottoli G,Paoletti M,et al.Identification of a predominant COPD phenotype in clinical practice.Respir Med,2008,102(3):367-376.
9 Fujimoto K,Kitaguchi Y,Kubo K,et al.Clinical analysis of chronic obstructive pulmonary disease phenotypes classified using highresolution computed tomography.Respirology,2006,11(6):731-740.
10Kitaguchi Y,Fujimoto K,Kubo K,et al.Characteristics of COPD phenotypes classified according to the findings of HRCT.Respir Med,2006,100(10):1742-1752.
11 李然,白澎,孙永昌,等.慢性阻塞性肺疾病肺气肿表型的临床与病理生理特征分析.中华结核和呼吸杂志,2011,34(11):857-858.
12Ley-Zaporozhan J,van Beek EJ.Imaging phenotypes of chronic obstructive pulmonary disease.J Magn Reson Imaging,2010,32(6):1340-1352.
13 凌芳,李瑛,胡成平.慢性阻塞性肺疾病肺气肿表型CT GOD评分与肺功能及其预后的相关性研究.中国实用内科杂志,2014,34 (S1):37-38.
14Barbosa EM,Song G,Tustison N,et al.Computational analysis of thoracic multidetector row HRCT for segmentation and quantification of small airway air trapping and emphysema in obstructive pulmonary disease.Acad Radiol,2011,18(10):1258-1269.
15 张伟宏,蔡柏蔷,王京兰,等.肺气肿的CT肺功能成像:CT技术与肺功能检查的对照研究.中华结核和呼吸杂志,2002,25(3):150-153.
16张敏,张盼盼,韩晓庆,等.不同程度慢性间歇低氧对大鼠齿状回Nogo-A和Ng R表达的影响.中华老年心脑血管病杂志,2015,17(5):522-525.
17 Mathur R,Cox IJ,Oatridge A,et al.Cerebral bioenergetics in stable chronic obstructive pulmonary disease.Am J Respir Crit Care Med,1999,160(6):1994-1999.
18Kirkil G,Tug T,Ozel E,et al.The evaluation of cognitive functions with P300 test for chronic obstructive pulmonary disease patients in attack and stable period.Clin Neurol Neurosurg,2007,109(7):553-560.
19 李力仙,江涛.单核/巨噬细胞及其趋化因子与脑缺血再灌注损伤.国外医学(脑血管疾病分册),2000,8(2):89-91.
20谭曦舒,李立群,胡玲玲,等.COPD患者血清MCP-1、SAA水平与认知功能的相关性研究.四川大学学报(医学版),2016,47(6):957-959.
21 Li JG,Chu J,Barrero C,et al.Homocysteine exacerbatesβ-amyloid pathology,tau pathology,and cognitive deficit in a mouse model of Alzheimer disease with plaques and tangles.Ann Neurol,2014,75(6):851-863.
22桂心,谢小红,张仁荣,等.高同型半胱氨酸血症与脑梗死合并慢性阻塞性肺疾病患者认知障碍的相关性及药物干预研究.中国生化药物杂志,2015,35(4):116-118.