阿尔茨海默病患者血清GGT、CTHRC1表达水平检测及临床意义

doi:10.11958/20221105

天津医药 ›› 2023, Vol. 51 ›› Issue (2): 216-220.doi: 10.11958/20221105

阿尔茨海默病患者血清GGT、CTHRC1表达水平检测及临床意义

陈俊¹(), 郑锦豪¹, 陈家良¹, 陈博²^,^△()

1 湖北省中医院/湖北中医药大学附属医院脑病科（邮编430061）
2 浙江省中医药研究院中医科

收稿日期:2022-07-14 修回日期:2022-10-09 出版日期:2023-02-15 发布日期:2023-02-24
通讯作者: ^△E-mail：chenbodoctor@163.com E-mail:cjun0711@163.com;chenbodoctor@163.com
作者简介:陈俊（1986），女，副主任医师，主要从事中西医结合防治脑病方面研究。E-mail：cjun0711@163.com
基金资助:
2020年浙江省自然科学基金面上资助项目(LGF21H270003)

Detection and clinical significance of serum GGT and CTHRC1 expression levels in patients with Alzheimer's disease

CHEN Jun¹(), ZHENG Jinhao¹, CHEN Jialiang¹, CHEN Bo²^,^△()

1 Department of Encephalopathy, Hubei Provincial Hospital of Traditional Chinese Medicine / Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan 430061, China
2 Department of Traditional Chinese Medicine, Zhejiang Institute of Traditional Chinese Medicine

Received:2022-07-14 Revised:2022-10-09 Published:2023-02-15 Online:2023-02-24
Contact: ^△E-mail：chenbodoctor@163.com E-mail:cjun0711@163.com;chenbodoctor@163.com

陈俊, 郑锦豪, 陈家良, 陈博. 阿尔茨海默病患者血清GGT、CTHRC1表达水平检测及临床意义[J]. 天津医药, 2023, 51(2): 216-220.

CHEN Jun, ZHENG Jinhao, CHEN Jialiang, CHEN Bo. Detection and clinical significance of serum GGT and CTHRC1 expression levels in patients with Alzheimer's disease[J]. Tianjin Medical Journal, 2023, 51(2): 216-220.

摘要/Abstract

摘要：

目的研究阿尔茨海默病（AD）患者血清γ-谷氨酰转移酶（GGT）和胶原蛋白三螺旋重复蛋白1（CTHRC1）表达及临床意义。方法以120例AD患者为AD组，以同期体检健康者60例为对照组。采用酶联免疫吸附试验检测各组血清GGT和CTHRC1表达及肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6，采用免疫比浊法检测血清超敏C反应蛋白（hs-CRP）水平。Pearson相关分析AD组血清GGT、CTHRC1表达与TNF-α、IL-1β、IL-6、CRP及简明精神状态量表（MMSE）评分的相关性。多因素Logistic回归分析影响AD发生的危险因素。受试者工作特征曲线分析血清GGT、CTHRC1水平对AD的诊断价值。结果 AD组患者血清GGT、CTHRC1、TNF-α、IL-6、IL-1β及hs-CRP水平高于对照组，MMSE评分明显低于对照组（均P<0.05）。AD组患者血清GGT、CTHRC1表达与TNF-α、IL-6、IL-1β及hs-CRP水平呈正相关，与MMSE评分呈负相关（均P<0.05）。GGT、CTHRC1水平升高及MMSE评分降低是影响AD发生的独立危险因素（P<0.05）。血清GGT和CTHRC1单独及联合检测诊断AD的曲线下面积（95%CI）分别为0.780（0.726~0.836）、0.728（0.705~0.810）、0.909（0.875~0.942）。联合检测对AD的诊断价值高于血清GGT和CTHRC1（Z分别为4.370和5.657，P<0.05）。结论 AD患者血清GGT和CTHRC1表达水平与患者炎症反应及认知程度有关，两者联合检测对AD具有较高的诊断价值。

关键词: 阿尔茨海默病, γ-谷氨酰转移酶1, 早期诊断, 胶原蛋白三螺旋重复序列因子1, 炎症反应

Abstract:

Objective To study the serum levels of gamma-glutamyl transferase (GGT) and collagen triple helix repeat containing 1 (CTHRC1) in Alzheimer's disease (AD) patients and their clinical significance. Methods A total of 120 AD patients diagnosed and treated in our hospital from January 2020 to January 2022 were selected as the AD group, and 60 healthy people who underwent physical examinations during the same period were selected as the control group. Enzyme-linked immunosorbent assay was used to detect serum expression levels of GGT, CTHRC1, tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in each group. Serum hypersensitive C-reactive protein (hs-CRP) was detected by immunoturbidimetry. Pearson correlation analysis was used to analyze the correlation between serum GGT, CTHRC1, TNF-α, IL-1β, IL-6, CRP and Concise Mental State Scale (MMSE) score in the AD group. Multivariate Logistic regression analysis was used to analyze risk factors affecting the occurrence of AD. Receiver operating curve analysis was used to analyze the diagnostic value of serum GGT and CTHRC1 levels in the diagnosis of AD. Results The serum levels of GGT, CTHRC1, TNF-α, IL-6, IL-1β and hs-CRP were significantly higher in the AD group than those in the control group, and the MMSE score was significantly lower than that in the control group (P<0.05). The expression levels of serum GGT and CTHRC1 were positively correlated with levels of TNF-α, IL-6, IL-1β and hs-CRP in the AD group, and were negatively correlated with the MMSE score (P<0.05). Increased GGT and CTHRC1 levels and decreased MMSE score were independent risk factors for the occurrence of AD (P<0.05). The areas under the curve (95%CI) of serum GGT and CTHRC1 alone and in combination for the diagnosis of AD were 0.780 (0.726-0.836), 0.728 (0.705-0.810) and 0.909 (0.875-0.942), respectively. The diagnostic value of serum GGT and CTHRC1 combined detection for AD was significantly higher than that of serum GGT and CTHRC1 single index detection (Z=4.370, 5.657, P<0.05). Conclusion The serum expression levels of GGT and CTHRC1 are related to the inflammatory response and cognitive level in AD patients. The combined detection of both has high diagnostic value for AD.

Key words: Alzheimer disease, gamma-glutamyl transferase 1, early diagnosis, collagen triple helix repeat factor 1, inflammatory response

中图分类号:

R749.16

图/表 6

参考文献 20

[1]	SCHELTENS P, DE STROOPER B, KIVIPELTO M, et al. Alzheimer's disease[J]. Lancet, 2021, 397(10284):1577-1590. doi:10.1016/S0140-6736(20)32205-4.
[2]	VEITCH D P, WEINER M W, AISEN P S, et al. Understanding disease progression and improving Alzheimer's disease clinical trials:Recent highlights from the Alzheimer's disease neuroimaging initiative[J]. Alzheimers Dement, 2019, 15(1):106-152. doi:10.1016/j.jalz.2018.08.005.
[3]	CORTI A, BELCASTRO E, DOMINICI S, et al. The dark side of gamma-glutamyltransferase (GGT):Pathogenic effects of an 'antioxidant' enzyme[J]. Free Radic Biol Med, 2020, 160(7):807-819. doi:10.1016/j.freeradbiomed.2020.09.005.
[4]	LEE Y B, HAN K, PARK S, et al. Gamma-glutamyl transferase variability and risk of dementia:A nationwide study[J]. Int J Geriatr Psychiatry, 2020, 35(10):1105-1114. doi:10.1002/gps.5332.
[5]	LI J, WANG Y, MA M, et al. Autocrine CTHRC1 activates hepatic stellate cells and promotes liver fibrosis by activating TGF-β signaling[J]. EBioMedicine, 2019, 40(7):43-55. doi:10.1016/j.ebiom.2019.01.009.
[6]	WANG H, DEY K K, CHEN P C, et al. Integrated analysis of ultra-deep proteomes in cortex,cerebrospinal fluid and serum reveals a mitochondrial signature in Alzheimer's disease[J]. Mol Neurodegener, 2020, 15(1):43-49. doi:10.1186/s13024-020-00384-6.
[7]	周小炫, 谢敏, 陶静, 等. 简易智能精神状态检查量表的研究和应用[J]. 中国康复医学杂志, 2016, 31(6):694-696,706.
	ZHOU X X, XIE M, TAO J, et al. Research and application of the simple intelligent mental state examination scale[J]. Chinese Journal of Rehabilitation Medicine, 2016, 31(6):694-696,706. doi:10.3969/j.issn.1001-1242.2016.06.019.
[8]	BUTTERFIELD D A, HALLIWELL B. Oxidative stress,dysfunctional glucose metabolism and Alzheimer disease[J]. Nat Rev Neurosci, 2019, 20(3):148-160. doi:10.1038/s41583-019-0132-6.
[9]	ZHUANG X X, WANG S F, TAN Y, et al. Pharmacological enhancement of TFEB-mediated autophagy alleviated neuronal death in oxidative stress-induced Parkinson's disease models[J]. Cell Death Dis, 2020, 11(2):128-135. doi:10.1038/s41419-020-2322-6.
[10]	LEE D H, BLOMHOFF R, JACOBS D R J R. Is serum gamma glutamyltransferase a marker of oxidative stress?[J]. Free Radic Res, 2004, 38(6):535-539. doi:10.1080/10715760410001694026.
[11]	GASECKA A, SIWIK D, GAJEWSKA M, et al. Early biomarkers of neurodegenerative and neurovascular disorders in diabetes[J]. J Clin Med, 2020, 9(9):2807-2812. doi:10.3390/jcm9092807.
[12]	ZHANG W, TANG Z, SHI Y, et al. Association between gamma-glutamyl transferase,total bilirubin and systemic lupus erythematosus in chinese women[J]. Front Immunol, 2021, 12(29):6824-6830. doi:10.3389/fimmu.2021.682400.
[13]	谢淑玲, 伍文彬, 彭丽燕, 等. 脑铁超载相关蛋白与阿尔茨海默病相关性[J]. 中国老年学杂志, 2015, 35(12):3456-3459.
	XIE S L, WU W B, PENG L Y, et al. Correlation between brain iron overload-related proteins and Alzheimer's disease[J]. Chinese Journal of Gerontology, 2015, 35(12):3456-3459. doi:10.3969/j.issn.1005-9202.2015.12.132.
[14]	BATSIOS G, NAJAC C, CAO P, et al. In vivo detection of gamma-glutamyl-transferase up-regulation in glioma using hyperpolarized gamma-glutamyl-[1-(13)C]glycine[J]. Sci Rep, 2020, 10(1):6244-6250. doi:10.1038/s41598-020-63160-y.
[15]	KIM Y G, PARK G M, LEE S B, et al. Association of gamma-glutamyl transferase with subclinical coronary atherosclerosis and cardiac outcomes in non-alcoholics[J]. Sci Rep, 2020, 10(1):17994-17999. doi:10.1038/s41598-020-75078-6.
[16]	MEI D, ZHU Y, ZHANG L, et al. The role of CTHRC1 in regulation of multiple signaling and tumor progression and metastasis[J]. Mediators Inflamm, 2020, 2020(12):9578-9585. doi:10.1155/2020/9578701.
[17]	BAI B, WANG X, LI Y, et al. Deep multilayer brain proteomics identifies molecular networks in alzheimer's disease progression[J]. Neuron, 2020, 105(6):975-991. doi:10.1016/j.neuron.2019.12.015.
[18]	KIM J, KIM J, KIM D W, et al. Wnt5a induces endothelial inflammation via beta-catenin-independent signaling[J]. J Immunol, 2010, 185(2):1274-1282. doi:10.4049/jimmunol.1000181.
[19]	ZHENG M, ZHOU Q, LIU X, et al. CTHRC1 overexpression promotes cervical carcinoma progression by activating the Wnt/PCP signaling pathway[J]. Oncol Rep, 2019, 41(3):1531-1538. doi:10.3892/or.2019.6963.
[20]	MYNGBAY A, BEXEITOV Y, ADILBAYEVA A, et al. CTHRC1:A new candidate biomarker for improved rheumatoid arthritis diagnosis[J]. Front Immunol, 2019, 12(10):1353-1360. doi:10.3389/fimmu.2019.01353.

组别	n	TC	TG	HDL-C	LDL-C
对照组	60	3.93±0.41	1.42±0.31	0.98±0.15	2.73±0.36
AD组	120	4.05±0.46	1.46±0.30	1.01±0.17	2.81±0.38
t或χ²		1.709	0.834	1.159	1.355

组别	n	TC	TG	HDL-C	LDL-C
对照组	60	3.93±0.41	1.42±0.31	0.98±0.15	2.73±0.36
AD组	120	4.05±0.46	1.46±0.30	1.01±0.17	2.81±0.38
t或χ²		1.709	0.834	1.159	1.355

组别		n	GGT（U/L）		CTHRC1（μg/L）		TNF-α（ng/L）
对照组		60	23.87±6.09		32.73±5.64		147.35±13.12
AD组		120	47.14±7.92		43.27±6.42		196.27±12.42
t			19.985^＊＊		10.800^＊＊		24.446^＊＊
组别	IL-6 （ng/L）			IL-1β （ng/L）		hs-CRP （ng/L）		MMSE 评分（分）
对照组	61.34±11.54			28.29±6.28		1.91±0.73		28.34±1.04
AD组	106.34±13.27			38.34±7.14		5.08±0.62		15.66±3.22
t	22.370^＊＊			9.256^＊＊		30.446^＊＊		29.702^＊＊

组别		n	GGT（U/L）		CTHRC1（μg/L）		TNF-α（ng/L）
对照组		60	23.87±6.09		32.73±5.64		147.35±13.12
AD组		120	47.14±7.92		43.27±6.42		196.27±12.42
t			19.985^＊＊		10.800^＊＊		24.446^＊＊
组别	IL-6 （ng/L）			IL-1β （ng/L）		hs-CRP （ng/L）		MMSE 评分（分）
对照组	61.34±11.54			28.29±6.28		1.91±0.73		28.34±1.04
AD组	106.34±13.27			38.34±7.14		5.08±0.62		15.66±3.22
t	22.370^＊＊			9.256^＊＊		30.446^＊＊		29.702^＊＊

参数	GGT	CTHRC1
TNF-α	0.418^＊	0.474^＊
IL-6	0.435^＊	0.414^＊
IL-1β	0.514^＊	0.437^＊
hs-CRP	0.515^＊	0.638^＊
MMSE评分	-0.649^＊	-0.657^＊

阿尔茨海默病患者血清GGT、CTHRC1表达水平检测及临床意义

Detection and clinical significance of serum GGT and CTHRC1 expression levels in patients with Alzheimer's disease

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变量	β	SE	Wald χ²	P	OR（95%CI）
TNF-α	0.113	0.082	1.899	0.802	1.120（0.953~1.315）
IL-6	0.139	0.094	2.187	0.121	1.149（0.956~1.382）
IL-1β	0.124	0.073	2.885	0.079	1.132（0.981~1.306）
hs-CRP	0.036	0.026	1.917	0.725	1.037（0.985~1.091）
GGT	0.145	0.054	7.210	<0.001	1.156（1.040~1.285）
CTHRC1	0.131	0.059	4.930	0.019	1.139（1.015~1.280）
MMSE评分	-0.298	0.111	7.208	<0.001	0.742（0.597~0.923）
常数项	-1.754	0.242	9.160	<0.001	0.571

指标	AUC（95%CI）	截断值	敏感度	特异度	约登指数
GGT	0.780（0.726~0.836）	45.37 U/L	0.802	0.624	0.426
CTHRC1	0.728（0.705~0.810）	40.16 μg/L	0.814	0.603	0.417
联合检测	0.909（0.875~0.942）	-	0.782	0.810	0.592

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