Fractalkine与慢性阻塞性肺疾病并肺源性心脏病患者氧化应激相关性及机制探讨

doi:10.3877/cma.j.issn.1674-6902.2017.01.013

中华肺部疾病杂志(电子版) ›› 2017, Vol. 10 ›› Issue (01) : 59 -63. doi: 10.3877/cma.j.issn.1674-6902.2017.01.013

所属专题：文献；

论著

Fractalkine与慢性阻塞性肺疾病并肺源性心脏病患者氧化应激相关性及机制探讨

向永红¹, 张云¹^,^†(

), 农智新¹, 梁世锋¹, 戴诗敏¹, 张润娟¹, 庞宗东¹, 雷艳梅¹, 潘海燕¹

^1. 530001　南宁，广西医科大学附属民族医院

收稿日期:2016-07-10 出版日期:2017-02-25
通信作者: 张云
基金资助:
广西自然科学基金资助项目(2012GXNSFAA053173); 广西壮族自治区卫生厅科研计划(Z2011412)

Investigate the mechanism and the relationship between fractalkine and oxidative stress of patients with COPD and pulmonary heart disease

Yonghong Xiang¹, Yun Zhang¹^,^†(), Zhixin Nong¹, Shifeng Liang¹, Shimin Dai¹, Runjuan Zhang¹, Zongdong Pang¹, Yanmei Lei¹, Haiyan Pan¹

^1. Department of Respiratory Medicine, Affiliated National Hospital of Guangxi Medical University, Nanning 530001, China

Received:2016-07-10 Published:2017-02-25
Corresponding author: Yun Zhang
About author:
Corresponding author: Zhang yun, Email: xiangyonghong319@sina.com

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引用本文：

向永红, 张云, 农智新, 梁世锋, 戴诗敏, 张润娟, 庞宗东, 雷艳梅, 潘海燕. Fractalkine与慢性阻塞性肺疾病并肺源性心脏病患者氧化应激相关性及机制探讨[J]. 中华肺部疾病杂志(电子版), 2017, 10(01): 59-63.

Yonghong Xiang, Yun Zhang, Zhixin Nong, Shifeng Liang, Shimin Dai, Runjuan Zhang, Zongdong Pang, Yanmei Lei, Haiyan Pan. Investigate the mechanism and the relationship between fractalkine and oxidative stress of patients with COPD and pulmonary heart disease[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2017, 10(01): 59-63.

目的

探讨Fractalkine(FKN)与慢性阻塞性肺疾病(COPD)并肺源性心脏病(简称肺心病)患者氧化应激状态的相关性及可能机制。

方法

64例AECOPD住院患者按是否合并肺心病、是否使用乙酰半胱氨酸(NAC)、COPD严重程度以及心功能分为8组，8例志愿者为正常对照组，测定各组患者住院次日、治疗后第10天血清各项指标，并检查心脏彩超、肺功能、CAT评分。

结果

血清FKN、NF-κB、OX-LDL及hsCRP水平在AECOPD的各组患者中均较正常对照组升高(P<0.05)，重症组及失代偿组升高明显(P<0.05)，肺心病组治疗前及治疗后均高于COPD组(P<0.05)，在COPD轻症干预组及肺心病代偿干预组治疗后下降明显(P<0.05)，SOD则相反。FEV₁在肺心病代偿干预组及COPD轻症干预组治疗后较治疗前升高(P<0.05)。肺动脉压在肺心病代偿干预组治疗前后有显著差异(P<0.05)，肺心病失代偿组较代偿组明显升高(P<0.05)，肺心病组与COPD组比较有显著差异(P<0.05)。CAT评分除在肺心病失代偿组外其它各组治疗前后均有显著差异(P<0.05)，肺心病组与COPD组比较有统计学差异(P<0.05)。治疗前8组患者血清FKN与CAT评分及NF-κB、OX-LDL、hsCRP、肺动脉压呈正相关(r＝0.417，0.521，0.401，0.456，0.395，P<0.05)，与SOD负相关(r＝－0.387, P<0.05)，与FEV₁无明显相关性(r＝0.215, P>0.05)。

结论

COPD并肺源性心脏病存在的氧化应激，与FKN密切相关，其机制可能系COPD持续低氧引起的氧化应激产物增多，激活NF-κB而促进FKN的生成和释放，NAC可能通过NF-κB途径降低FKN的生成，对早期肺心病的预防有一定作用。

关键词: Fractalkine, 肺疾病，慢性阻塞性, 氧化应激, C反应蛋白

Objective

To investigate the mechanism and the relationship between fractalkine and oxidative stress of patients with COPD and pulmonary heart disease.

Methods

64 patients with AECOPD were divided into the following 8 groups according to whether merger pulmonary heart disease, whether using NAC, Cardiac function and GOLD classification of COPD disease severity. 8 healthy volunteers were selected as control group. Blood samples before and 10 days after treatment were collected to detect the level of all serum indicators, Color Doppler echocardiography, lung function and CAT score were also examined.

Results

Levels of FKN, NF-κB, OX-LDL and hsCRP in different groups of AECOPD patients were higher than healthy control (P<0.05) and all of them were higher in severe group than mild group (P<0.05). Also, before and after treatment, those in pulmonary heart disease group were higher than COPD group, but decreased significantly in COPD+ NAC group and mild cases of pulmonary heart disease + NAC group (P<0.05). SOD, on the contrary. Administration of NAC resulted in elevated FEV₁ in mild cases of COPD group and pulmonary heart disease group (P<0.05). Pulmonary arterial pressure changed strikingly in the mild cases of pulmonary heart disease + NAC group after treatment (P<0.05), Compared to mild cases of pulmonary heart disease patients, higher pulmonary arterial pressure existed in severe cases. Compared with COPD group, the pulmonary artery pressure of pulmonary heart disease group was significantly higher (P<0.05). Besides, in severe cases of pulmonary heart disease group, CAT score in other groups altered significantly before and after treatment (P<0.05). Also, marked difference was seen between COPD group and pulmonary heart disease group(P<0.05); The level of FKN was positively correlated with CAT score, NF-κB, OX-LDL, hsCRP and pulmonary artery pressure (r=0.417, 0.521, 0.401, 0.456, 0.395, P<0.05), and negatively correlated with SOD(r=-0.387, P<0.05), while had no obvious correlation with FEV₁ (r=0.215, P>0.05).

Conclusions

Oxidative stress in patients with COPD and cor pulmonale is closely related to FKN, Hypoxemia causes an increase in ROS, which activates the NF-κB and promotes FKN to generate and release. NAC could inhibit ROS generation, which prevents the activation of NF-κB and reduces the production of FKN. Our results show that NAC may be helpful for prevention of COPD and pulmonary heart disease in early stage.

Key words: Fractalkine, Chronic obstructive pulmonary disease, Oxidative stress, C reactive protein

表1 各组FKN、hsCRP、NF-κB、SOD、OX-LDL、FEV₁%、平均肺动脉压(mPAP)、CAT评分结果(±s)

组　别	例数	FKN(pg/ml)		hsCRP(nmol/L)		FEV₁%		CAT评分(分)
组　别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
COPD轻症对照组	11	336.33±69.98^a	257.99±95.07^ab	8.31±0.54^a	7.94±0.79^a	57.67±7.46^a	59.39±10.39^a	18±5^e	12±3^eb
COPD轻症干预组	10	323.47±59.94^a	200.12±43.52^abi	9.04±0.67^a	4.67±0.53^abi	58.09±9.86^a	69.28±12.04^ab	17±4^e	10±2^ab
COPD重症对照组	5	584.91±87.45^ec	496.51±67.60^eg	15.67±4.05^e	13.60±3.05^e	35.56±9.37^e	38.93±10.33^e	28±7^e	22±5^eb
COPD重症干预组	6	601.08±77.35^ec	521.70±52.38^eg	16.91±3.99^e	12.22±3.29^e	33.27±10.31^e	36.73±9.03^e	29±5^e	15±6^ebi
肺心病代偿对照组	9	675.34±174.49^e	598.41±134.24^e	15.20±3.01^e	13.07±2.84^e	55.73±10.23^a	57.78±12.39^a	22±6^e	15±6^eb
肺心病代偿干预组	10	626.93±167.16^e	490.12±114.43^eb	14.33±4.56^e	8.01±2.56^eb	57.55±13.79^a	68.99±12.89^ab	23±4^e	11±4^ebi
肺心病失代偿对照组	7	892.36±219.48^ed	855.30±209.11^ed	24.27±6.43^ed	19.43±5.48^ed	40.52±8.33^a	44.86±12.39^a	31±7^e	28±6^e
肺心病失代偿干预组	6	903.38±228.56^ed	812.77±219.27^ed	25.63±5.77^ed	19.97±5.37^ed	42.12±9.56^a	49.29±12.97^a	30±7^e	25±5^e
正常对照组	8	164.63±55.13	153.29±63.40	2.09±0.56	1.96±0.89	88.13±8.49	86.99±9.29	0	0
F值	?	18.26	15.34	21.12	25.17	9.28	10.74	30.38	28.64
P值	?	<0.05	<0.05	<0.01	<0.01	<0.05	<0.05	<0.001	<0.001
组　别	例数	NF-κB (ng/ml)		SOD (NU/ml)		OX-LDL (μg/L)		平均肺动脉压(mmHg)
组　别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
COPD轻症对照组	11	9.31±0.78^a	7.99±0.43^a	123.24±40.11^a	126.43±43.23^a	477.34±139.44^a	393.55±69.57^a	22.54±2.52	20.76±3.28
COPD轻症干预组	10	10.04±0.54^a	5.34±0.63^abi	121.48±45.63^a	145.35±38.21^aib	465.68±146.77^a	315.68±78.36^abi	23.78±2.78	21.35±2.12
COPD重症对照组	5	16.36±1.45^ac	13.51±0.65^ac	73.47±26.55^ac	78.58±21.32^ac	688.22±265.34^a	633.53±211.34^a	24.33±3.45	25.25±3.03
COPD重症干预组	6	15.99±1.92^ac	10.27±1.24^ac	74.39±30.22^ac	81.35±33.64^ac	672.35±252.21^a	618.37±221.38^a	23.79±2.96	21.36±2.87
肺心病代偿对照组	9	14.46±2.03^a	12.77±1.64^a	79.26±25.39^a	86.74±27.95^a	701.23±211.34^a	672.22±234.51^a	24.74±3.67	22.48±2.99
肺心病代偿干预组	10	15.87±2.77^a	10.75±1.25^ab	81.49±41.23^a	98.72±32.77^ab	690.46±238.26^a	550.92±179.31^ab	25.22±2.77	20.01±1.87^b
肺心病失代偿对照组	7	20.57±3.47^ad	18.86±2.47^ad	65.67±47.29^ad	71.24±32.31^ad	802.82±229.88^ad	814.58±235.62^ad	31.64±4.01^d	29.36±3.72^d
肺心病失代偿干预组	6	20.99±2.73^ad	16.94±3.68^ad	63.33±30.21^ad	75.88±35.63^ad	810.55±233.56^ad	774.36±217.89^ad	32.21±3.38^d	28.25±2.93^d
正常对照组	8	4.43±0.28	4.91±0.07	175.84±80.12	178.37±75.35	275.35±68.36	267.89±62.19	16.75±2.66	16±3
F值	?	12.26	10. 66	9.25	8.23	10.56	9.38	8.53	7.59
P值	?	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05

表1 各组FKN、hsCRP、NF-κB、SOD、OX-LDL、FEV₁%、平均肺动脉压(mPAP)、CAT评分结果(±s)

组　别	例数	FKN(pg/ml)		hsCRP(nmol/L)		FEV₁%		CAT评分(分)
组　别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
COPD轻症对照组	11	336.33±69.98^a	257.99±95.07^ab	8.31±0.54^a	7.94±0.79^a	57.67±7.46^a	59.39±10.39^a	18±5^e	12±3^eb
COPD轻症干预组	10	323.47±59.94^a	200.12±43.52^abi	9.04±0.67^a	4.67±0.53^abi	58.09±9.86^a	69.28±12.04^ab	17±4^e	10±2^ab
COPD重症对照组	5	584.91±87.45^ec	496.51±67.60^eg	15.67±4.05^e	13.60±3.05^e	35.56±9.37^e	38.93±10.33^e	28±7^e	22±5^eb
COPD重症干预组	6	601.08±77.35^ec	521.70±52.38^eg	16.91±3.99^e	12.22±3.29^e	33.27±10.31^e	36.73±9.03^e	29±5^e	15±6^ebi
肺心病代偿对照组	9	675.34±174.49^e	598.41±134.24^e	15.20±3.01^e	13.07±2.84^e	55.73±10.23^a	57.78±12.39^a	22±6^e	15±6^eb
肺心病代偿干预组	10	626.93±167.16^e	490.12±114.43^eb	14.33±4.56^e	8.01±2.56^eb	57.55±13.79^a	68.99±12.89^ab	23±4^e	11±4^ebi
肺心病失代偿对照组	7	892.36±219.48^ed	855.30±209.11^ed	24.27±6.43^ed	19.43±5.48^ed	40.52±8.33^a	44.86±12.39^a	31±7^e	28±6^e
肺心病失代偿干预组	6	903.38±228.56^ed	812.77±219.27^ed	25.63±5.77^ed	19.97±5.37^ed	42.12±9.56^a	49.29±12.97^a	30±7^e	25±5^e
正常对照组	8	164.63±55.13	153.29±63.40	2.09±0.56	1.96±0.89	88.13±8.49	86.99±9.29	0	0
F值	?	18.26	15.34	21.12	25.17	9.28	10.74	30.38	28.64
P值	?	<0.05	<0.05	<0.01	<0.01	<0.05	<0.05	<0.001	<0.001
组　别	例数	NF-κB (ng/ml)		SOD (NU/ml)		OX-LDL (μg/L)		平均肺动脉压(mmHg)
组　别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
COPD轻症对照组	11	9.31±0.78^a	7.99±0.43^a	123.24±40.11^a	126.43±43.23^a	477.34±139.44^a	393.55±69.57^a	22.54±2.52	20.76±3.28
COPD轻症干预组	10	10.04±0.54^a	5.34±0.63^abi	121.48±45.63^a	145.35±38.21^aib	465.68±146.77^a	315.68±78.36^abi	23.78±2.78	21.35±2.12
COPD重症对照组	5	16.36±1.45^ac	13.51±0.65^ac	73.47±26.55^ac	78.58±21.32^ac	688.22±265.34^a	633.53±211.34^a	24.33±3.45	25.25±3.03
COPD重症干预组	6	15.99±1.92^ac	10.27±1.24^ac	74.39±30.22^ac	81.35±33.64^ac	672.35±252.21^a	618.37±221.38^a	23.79±2.96	21.36±2.87
肺心病代偿对照组	9	14.46±2.03^a	12.77±1.64^a	79.26±25.39^a	86.74±27.95^a	701.23±211.34^a	672.22±234.51^a	24.74±3.67	22.48±2.99
肺心病代偿干预组	10	15.87±2.77^a	10.75±1.25^ab	81.49±41.23^a	98.72±32.77^ab	690.46±238.26^a	550.92±179.31^ab	25.22±2.77	20.01±1.87^b
肺心病失代偿对照组	7	20.57±3.47^ad	18.86±2.47^ad	65.67±47.29^ad	71.24±32.31^ad	802.82±229.88^ad	814.58±235.62^ad	31.64±4.01^d	29.36±3.72^d
肺心病失代偿干预组	6	20.99±2.73^ad	16.94±3.68^ad	63.33±30.21^ad	75.88±35.63^ad	810.55±233.56^ad	774.36±217.89^ad	32.21±3.38^d	28.25±2.93^d
正常对照组	8	4.43±0.28	4.91±0.07	175.84±80.12	178.37±75.35	275.35±68.36	267.89±62.19	16.75±2.66	16±3
F值	?	12.26	10. 66	9.25	8.23	10.56	9.38	8.53	7.59
P值	?	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05

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Investigate the mechanism and the relationship between fractalkine and oxidative stress of patients with COPD and pulmonary heart disease

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Investigate the mechanism and the relationship between fractalkine and oxidative stress of patients with COPD and pulmonary heart disease