帕金森病患者血清ANGPTL2、NRG-1水平及临床意义

doi:10.11958/20252282

摘要/Abstract

摘要：

目的探讨帕金森病（PD）患者血清血管生成素样蛋白2（ANGPTL2）、神经生长因子-1（NRG-1）水平的临床意义。方法选取PD患者274例及健康志愿者266例分别作为观察组和对照组。采用蒙特利尔认知评估量表（MoCA）对PD患者认知功能进行评估，将其分为认知障碍组（MoCA评分<26分，n=161）和无认知障碍组（MoCA评分≥26分，n=113）。采用Hoehn-Yahr（H-Y）分期对PD患者疾病严重程度进行分级，将其分为H-Y 1—2期118例、H-Y 3期94例和H-Y 4期62例。采用酶联免疫吸附试验检测2组血清ANGPTL2、NRG-1水平；采用Pearson相关分析PD患者血清ANGPTL2与NRG-1水平的相关性；Logistic回归分析PD的影响因素；受试者工作特征（ROC）曲线评估二者对PD的诊断效能。结果观察组PD患者受教育年限、血清NRG-1水平低于对照组，PD家族史比例、血清ANGPTL2水平高于对照组（P<0.05）；认知障碍组血清ANGPTL2水平高于无认知障碍组，NRG-1水平低于无认知障碍组（P<0.05）；H-Y 1—2、3、4期PD患者血清ANGPTL2水平依次升高，血清NRG-1水平依次降低（P<0.05）。PD患者血清ANGPTL2与NRG-1水平呈负相关（r=-0.373，P<0.001）。Logistic回归分析显示，血清ANGPTL2水平升高是影响PD发生的独立危险因素，血清NRG-1水平升高是影响PD发生的独立保护因素（P<0.05）。ROC曲线分析显示，血清ANGPTL2、NRG-1水平及二者联合诊断PD的曲线下面积分别为0.689（95%CI：0.645~0.733）、0.717（95%CI：0.674~0.760）、0.768（95%CI：0.729~0.808），二者联合的诊断效能优于单一指标。结论 PD患者血清ANGPTL2水平升高、NRG-1水平降低，二者变化程度与疾病严重程度相关，联合检测此两项指标对PD的诊断具有重要临床价值。

关键词: 帕金森病, 血管生成素样蛋白质类, 神经生长因子类, ANGPTL2, NRG-1

Abstract:

Objective To explore the clinical significance of serum angiopoietin-like protein 2 (ANGPTL2) and neuregulin-1 (NRG-1) levels in patients with Parkinson's disease (PD). Methods A total of 274 PD patients and 266 healthy volunteers were selected as the observation group and the control group, respectively. The Montreal Cognitive Assessment (MoCA) was used to evaluate the cognitive function of PD patients, and patients were divided into the cognitive impairment group (MoCA score <26, n=161) and the non-cognitive impairment group (MoCA score ≥26, n=113). The Hoehn-Yahr (H-Y) scale was used to grade the severity of PD, and patients were classified into the H-Y stages 1-2 (118 cases), the stage 3 (94 cases) and the stage 4 (62 cases). Enzyme-linked immunosorbent assay (ELISA) was used to measure serum ANGPTL2 and NRG-1 levels in both groups. Pearson correlation analysis was used to examine the relationship between serum ANGPTL2 and NRG-1 levels in PD patients. Logistic regression was used to analyze influencing factors of PD. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of both markers for PD. Results The serum NRG-1 and education years of PD patients were prominently lower in the observation group than those of the healthy group (P<0.05), and the serum ANGPTL2 and proportion of PD family history were prominently higher in the observation group than those of the control group (P<0.05). The serum ANGPTL2 levels were higher in the cognitive impairment group than those of the non cognitive impairment group (P<0.05), and NRG-1 prominently lower than the non cognitive impairment group (P<0.05). The serum ANGPTL2 levels increased successively in PD patients with H-Y stages 1-2, 3 and 4, and serum NRG-1 lvevels decreased successively (P<0.05). The serum levels of ANGPTL2 and NRG-1 were negatively correlated in PD patients (r=-0.373, P<0.001). Logistic regression analysis showed that elevated serum ANGPTL2 levels were the independent risk factors affecting the occurrence of PD, while high level of NRG-1 was an independent protective factor for PD (P<0.05). The area under the curve (AUC) of serum ANGPTL2, NRG-1 and their combined diagnosis for PD was 0.689 (95%CI: 0.645-0.733), 0.717 (95%CI: 0.674-0.760) and 0.768 (95%CI: 0.729-0.808), respectively. The combined diagnosis of the two was superior to the individual prediction of ANGPTL2 and NRG-1 (Z_{ANGPTL2-combination}=2.608, Z_{NRG-1-combination}=2.017, P=0.009, P=0.044). Conclusion PD patients have elevated serum ANGPTL2 levels and reduced NRG-1 levels, with the extent of these changes correlating with disease severity. Combined testing of these two indicators has important clinical value for the diagnosis of PD.

Key words: Parkinson disease, angiopoietin-like proteins, nerve growth factors, ANGPTL2, NRG-1

中图分类号:

R742.5

图/表 7

参考文献 20

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组别		n	年龄/岁		男性		BMI/ （kg/m²）		吸烟史
对照组		266	59.46±7.01		147（55.26）		21.45±2.17		51（19.17）
观察组		274	59.73±6.75		161（58.76）		21.39±2.05		56（20.44）
t或χ²			0.456		0.673		0.330		0.136
组别	饮酒史			收缩压/ mmHg		舒张压/mmHg		受教育年限/年		PD 家族史
对照组	101（37.97）			126.49±15.54		75.28±9.46		11.04±1.54		12（4.51）
观察组	119（43.43）			128.74±19.25		76.23±8.72		7.19±1.28		34（12.41）
χ²或t	1.667			1.492		1.214		31.631^＊		10.802^＊

组别		n	年龄/岁		男性		BMI/ （kg/m²）		吸烟史
对照组		266	59.46±7.01		147（55.26）		21.45±2.17		51（19.17）
观察组		274	59.73±6.75		161（58.76）		21.39±2.05		56（20.44）
t或χ²			0.456		0.673		0.330		0.136
组别	饮酒史			收缩压/ mmHg		舒张压/mmHg		受教育年限/年		PD 家族史
对照组	101（37.97）			126.49±15.54		75.28±9.46		11.04±1.54		12（4.51）
观察组	119（43.43）			128.74±19.25		76.23±8.72		7.19±1.28		34（12.41）
χ²或t	1.667			1.492		1.214		31.631^＊		10.802^＊

组别	n	ANGPTL2/（μg/L）	NRG-1/（ng/L）
对照组	266	9.46±1.95	286.77±45.39
观察组	274	10.82±2.08	259.10±41.26
t		7.833^＊	7.417^＊

组别	n	ANGPTL2/（μg/L）	NRG-1/（ng/L）
对照组	266	9.46±1.95	286.77±45.39
观察组	274	10.82±2.08	259.10±41.26
t		7.833^＊	7.417^＊

组别	n	ANGPTL2/（μg/L）	NRG-1/（ng/L）
无认知障碍组	113	7.38±1.97	282.86±37.51
认知障碍组	161	13.24±4.28	242.43±41.50
t		13.575^＊	8.256^＊