自分泌运动因子和溶血磷脂酸受体3在慢性阻塞性肺疾病患者血清及肺组织中的表达及其意义

doi:10.13481/j.1671-587X.20250123

Abstract

Abstract:

Objective To discuss the expressions of autotaxin （ATX） and lysophosphatidic acid receptor 3 （LPA3） in serum and lung tissue of the chronic obstructive pulmonary disease （COPD） patients， and to clarify the role of ATX and LPA3 in the occurrence and development of COPD. Methods A total of 40 COPD patients were collected and brought into acute exacerbation of COPD group （AECOPD group）； after treatment， those stabilized patients were included in COPD stable group （n=40）； additionally， 40 healthy individuals were recruited as control group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the ATX levels in the serum of the subjects in various groups. Another 80 patients who underwent lobectomy were divided into COPD smoking group （CS group， n=20）， COPD non-smoking group （CNS group， n=20）， non-COPD smoking group （HS group， n=20）， and non-COPD non-smoking group （HNS group， n=20）. The general informations of the subjects in various groups were collected. HE staining was used to observe the pathomorphology of lung tissue of the patients in various groups；immunohistochemical staining was used to detect the expression levels of ATX and LPA3 proteins in lung tissue of the patients in various groups；real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of ATX and LPA3 mRNA in lung tissue of the patients in various groups；Pearson correlation analysis was used to evaluate the correlations of continuous variables with normal distribution， and Spearman correlation analysis was used to evaluate the correlations of other variables. Results Compared with control group， the percentage of forced expiratory volume in the first second to predicted value （FEV1%pred） and the percentage of forced expiratory volume in the first second to forced vital capacity （FEV1/FVC） of the patients in COPD stable group were significantly decreased （P<0.05）. Compared with COPD stable group and control group， the level of ATX in serum of the patients in AECOPD group was increased （P<0.05）； compared with control group， the level of ATX in serum of the patients in COPD stable group was increased （P<0.05）. The serum ATX level of the patients in AECOPD group was positively correlated with COPD Assessment Test （CAT） scores （r=0.581， P<0.001） and showed no correlations with smoking history， white blood cells （WBC）， percentage of neutrophils （NEUT%）， neutrophil to lymphocyte ratio （NLR）， and body mass index （BMI）（P>0.05）. The serum ATX level of the patients in COPD stable group was positively correlated with WBC and CAT score （r=0.384， P=0.014； r=0.463， P=0.003） and negatively correlated with FEV1%pred and FEV1/FVC （r=-0.393， P=0.012； r=-0.353， P=0.025）. Compared with CS group and CNS group， the FEV1%pred and FEV1/FVC of the patients in HS group and HNS group were increased （P<0.05）. The immunohistochemical staining results showed that compared with CS group， the expression levels of ATX and LPA3 proteins in lung tissue of the patients in HS group and HNS group were decreased （P<0.05）. Compared with CNS group， the expression levels of ATX and LPA3 proteins in lung tissue of the patients in HS group and HNS group were decreased （P<0.05）. The RT-qPCR results showed that compared with CS group， the expression levels of ATX and LPA3 mRNAs in lung tissue of the patients in HS group and HNS group were decreased （P<0.05）； compared with CNS group， the expression levels of ATX and LPA3 mRNAs in lung tissue of the patients in HS group and HNS group were decreased （P<0.05）. The correlation analysis results showed that the expression level of ATX protein in lung tissue of the COPD patients was positively correlated with the expression level of LPA3 protein （r=0.723， P<0.001）. Conclusion The expression levels of ATX and LPA3 mRNA and proteins in lung tissue of the COPD patients are increased. The serum ATX levels in both AECOPD group and COPD stable group are increased， suggesting that these factors may be involved in the inflammatory response of COPD， promoting its occurrence and development.

Key words: Chronic obstructive pulmonary disease, Autotaxin motility factor, Lysophosphatidic acid, Receptor, Smoking

CLC Number:

R563.9

Peiqin JIANG,Zheng ZHANG,Zhong HUANG,Xianling LU. Expressions of autotaxin and lysophosphatidic acid receptor 3 in serum and lung tissue of patients with chronic obstructive pulmonary disease and their significances[J].Journal of Jilin University(Medicine Edition), 2025, 51(1): 191-201.

Figures/Tables 10

Tab.1

Clinical data of subjects in control group and COPD stable group"

Group	Age （x±s， year）	BMI （x±s， kg·m^-2）	FEV1%pred （x±s， η/%）	FEV1/FVC （x±s， η/%）	Percentage of male [n(η/%)]	Percentage of smoking [n(η/%）]
Control	69.70±7.40	24.18±2.30	97.10±6.82	78.05±3.56	19（47.5）	13（32.5）
COPD stable	69.85±7.32	24.91±2.38	48.88±6.55	51.08±7.47	23（57.5）	18（45.0）
t/χ²	0.091	1.389	$-$ 32.251	$-$ 20.624	0.802	1.317
P	0.928	0.169	<0.001	<0.001	0.370	0.251

Tab.1

Tab.2

Tab.3

Fig. 1

Tab.4

Bosken scores, MLI， and MAN of lung tissue of patients in various groups"

Group	Bosken score	MLI（l/mm）	MAN（ $m m - 2$ ）
CS	17.75±1.65	0.20±0.40	31.81±4.92
CNS	14.35±1.63^*	0.18±0.03	33.97±3.55
HS	6.15±1.23^*△	0.12±0.04^*△	53.47±12.64^*△
HNS	2.60±1.10^*△#	0.11±0.03^*△	56.14±11.96^*△
F	489.311	40.068	37.022
P	<0.001	<0.001	<0.001

Tab.4

Fig. 2

Fig. 3

Fig. 4

Fig. 5

Tab.5

Correlations between expression levels of ATX and LPA3 proteins and other indicators in lung tissue of COPD patients"

Index	ATX		LPA3
Index	r	P	r	P
FEV1%pred	$-$ 0.374	0.017	$-$ 0.286	0.074
FEV1/FVC	$-$ 0.370	0.019	$-$ 0.271	0.090
Bosken score	0.493	0.001	0.576	<0.001
MLI	0.375	0.017	0.378	0.016
MAN	$-$ 0.396	0.011	$-$ 0.395	0.012
LPA3	0.723	<0.001	-	-

Tab.5

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Group	Age （x±s， year）	BMI （x±s， kg·m^-2）	SI （x±s）	FEV1%pred （x±s， η/%）	FEV1/FVC （x±s， η/%）	Percentage of male [n(η/%)]
CS	64.10±9.88	24.43±1.59	620.00±311.47	77.65±7.58	62.85±4.11	14（70.0）
CNS	64.20±7.27	23.59±1.71	-	77.45±8.09	63.25±4.23	11（55.0）
HS	63.50±8.63	24.74±2.02	608.00±334.81	95.60±9.13^*△	76.70±3.92^*△	14（70.0）
HNS	62.45±8.68	24.52±2.04	-	100.40±11.86^*△	78.90±4.96^*△	10（50.0）
F/χ²	0.172	1.501	0.014	33.025	78.503	2.686
P	0.915	0.221	0.907	<0.001	<0.001	0.443

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Expressions of autotaxin and lysophosphatidic acid receptor 3 in serum and lung tissue of patients with chronic obstructive pulmonary disease and their significances

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Index	AECOPD group		COPD stable group
Index	r	P	r	P
Smoking	0.052	0.749	0.107	0.512
WBC	0.110	0.499	0.384	0.014
NEUT%	0.074	0.650	0.054	0.738
NLR	0.046	0.776	-0.020	0.902
BMI	0.043	0.791	0.245	0.127
CAT	0.581	<0.001	0.463	0.003
FEV1%pred	-	-	-0.393	0.012
FEV1/FVC	-	-	-0.353	0.025