血清TRPV1、DNMT1、SFRP5与过敏性鼻炎疾病严重程度的相关性

doi:10.11958/20260009

摘要/Abstract

摘要：

目的探讨过敏性鼻炎（AR）患者血清瞬时受体电位香草酸亚型1（TRPV1）、DNA甲基化转移酶1（DNMT1）、分泌型卷曲相关蛋白5（SFRP5）水平与病情进展的相关性。方法选取2022年6月—2025年6月就诊于南阳市中心医院的AR患者120例为研究对象，根据鼻症状总积分表（TNSS）将患者分为轻中症AR组（75例，TNSS总分≤8分）和重症AR组（45例，TNSS总分≥9分）。采用酶联免疫吸附试验（ELISA）检测血清TRPV1、DNMT1、SFRP5及免疫球蛋白E（IgE）水平。采用Pearson相关分析血清TRPV1、DNMT1、SFRP5水平与TNSS评分、血清IgE水平的相关性。采用多因素Logistic回归分析血清TRPV1、DNMT1、SFRP5水平对AR病情进展的影响。绘制受试者工作特征（ROC）曲线评估血清TRPV1、DNMT1、SFRP5水平单独及联合预测重症AR的价值。结果与轻中症AR组相比，重症AR组合并哮喘比例、TNSS评分、血清IgE、TRPV1、DNMT1水平升高，血清SFRP5水平降低（P<0.01）。血清TRPV1、DNMT1水平与TNSS评分、IgE均呈正相关，血清SFRP5水平与TNSS评分、IgE均呈负相关（P<0.01）。多因素Logistic回归分析显示，血清TRPV1（OR=1.844，95%CI：1.283~2.650）、DNMT1（OR=2.356，95%CI：1.552~3.577）水平升高及SFRP5（OR=0.865，95%CI：0.798~0.937）水平降低是AR患者进展为重症的独立危险因素（P<0.05）。ROC曲线分析显示，血清TRPV1、DNMT1、SFRP5单独及联合预测重症AR的曲线下面积（AUC）分别为0.775（95%CI：0.690~0.846）、0.844（95%CI：0.766~0.904）、0.808（95%CI：0.727~0.875）、0.921（95%CI：0.858~0.963），联合预测的AUC高于各单指标（P<0.05）。结论重症AR患者血清TRPV1、DNMT1水平升高，SFRP5水平降低，三者水平变化与AR病情密切相关，联合检测可用于早期预测病情进展。

关键词: 鼻炎, 变应性, TRPV阳离子通道, DNA（胞嘧啶-5-）-甲基转移酶1, 分泌型卷曲相关蛋白5

Abstract:

Objective To investigate the correlation between serum transient receptor potential vanilloid 1 (TRPV1), DNA methyltransferase 1 (DNMT1) and secreted frizzled related protein 5 (SFRP5) with the severity of allergic rhinitis (AR) in patients. Methods A total of 120 AR patients treated in our hospital from June 2022 to June 2025 were enrolled and categorized into the mild to moderate AR group (75 cases, TNSS total score≤8) and the severe AR group (45 cases, TNSS total score≥9) based on the total nasal symptom score (TNSS). Serum levels of TRPV1, DNMT1, SFRP5 and immunoglobulin E(IgE) were measured using enzyme-linked immunosorbent assay (ELISA) kits. Pearson correlation analysis was used to evaluate the correlation of serum TRPV1, DNMT1 and SFRP5 levels with TNSS score and serum IgE level. Multivariate Logistic regression analysis was performed to assess the impact of serum TRPV1, DNMT1 and SFRP5 levels on AR progression. Receiver operating characteristic (ROC) curve was plotted to evaluate the value of serum TRPV1, DNMT1 and SFRP5 levels alone and in combination for predicting severe AR. Results Compared with the mild to moderate AR group, the proportion of patients with concomitant asthma, TNSS scores and serum levels of IgE, TRPV1 and DNMT1 increased in the severe AR group, and serum level of SFRP5 was decreased (P<0.01). Serum levels of TRPV1 and DNMT1 were positively correlated with TNSS score and IgE (P<0.01), while the serum level SFRP5 was negatively correlated with TNSS score and IgE (P<0.01). Multivariate Logistic regression analysis showed that elevated serum TRPV1 (OR=1.844, 95%CI: 1.283-2.650) and DNMT1 (OR=2.356, 95%CI: 1.552-3.577) levels, and decreased SFRP5 (OR=0.865, 95%CI: 0.798-0.937) level were independent risk factors for progression of severe cases in AR patients (P<0.05). The AUC values of single and combined predictions of serum TRPV1, DNMT1 and SFRP5 levels for severe AR were 0.775 (95%CI: 0.690-0.846), 0.844 (95%CI: 0.766-0.904), 0.808 (95%CI: 0.727-0.875) and 0.921 (95%CI: 0.858-0.963), respectively. Compared with single indicator prediction, the combined prediction value of three indicators was higher (P<0.05). Conclusion In severe AR patients, serum TRPV1 and DNMT1 levels are elevated, while SFRP5 level is reduced. The alterations in these three biomarkers are closely associated with AR disease severity. Combined detection of the three indicators can be used for early prediction of disease progression.

Key words: rhinitis, allergic, TRPV cation channels, DNA (cytosine-5-)-methyltransferase 1, SFRP5

中图分类号:

R765.21

图/表 6

参考文献 21

[1]	Rosenfield L, Keith P K, Quirt J, et al. Allergic rhinitis[J]. Allergy Asthma Clin Immunol, 2024, 20(Suppl 3):74. doi:10.1186/s13223-024-00923-6.
[2]	Green R J, Van Niekerk A, Mcdonald M, et al. Acute allergic rhinitis[J]. S Afr Fam Pract, 2020, 62(1):a5154-a5159. doi:10.4102/safp.v62i1.5154.
[3]	Xiao C, Feng L, Yang W. Inhibition of dendritic cell autophagy alleviates the progression of allergic rhinitis by inhibiting Th1/Th2/Th17 immune imbalance and inflammation[J]. Histol Histopathol, 2025, 40(2):237-247. doi:10.14670/hh-18-769.
[4]	Liu M P, Jia X H, Liu H M, et al. Role of TRPV1 in respiratory disease and association with traditional Chinese medicine:a literature review[J]. Biomed Pharmacother, 2022, 155:113676. doi:10.1016/j.biopha.2022.113676.
[5]	Liu J, Jiang X, Liu K, et al. Role of LINC00240 on T-helper 9 differentiation in allergic rhinitis through influencing DNMT1-dependent methylation of PU.1[J]. Immunol Res, 2024, 72(2):197-211. doi:10.1007/s12026-023-09435-8.
[6]	Shi Z, Zhao T, Li D, et al. Silencing of forkhead box C1 reduces nasal epithelial barrier damage in mice with allergic rhinitis via epigenetically upregulating secreted frizzled-related protein 5[J]. Mol Immunol, 2024, 168:51-63. doi:10.1016/j.molimm.2024.02.011.
[7]	中华耳鼻咽喉头颈外科杂志编辑委员会鼻科组, 中华医学会耳鼻咽喉头颈外科学分会鼻科学组. 中国变应性鼻炎诊断和治疗指南(2022年,修订版)[J]. 中华耳鼻咽喉头颈外科杂志, 2022, 57(2):106-129.
	Subspecialty Group of Rhinology,Editorial Board of Chinese Journal of Otorhinolaryngology Head and Neck Surgery, Subspecialty Group of Rhinology,Society of Otorhinolaryngology Head and Neck Surgery,Chinese Medical Association. Chinese guideline for diagnosis and treatment of allergic rhinitis (2022,revision)[J]. Chin J Otorhinolaryngol Head Neck Surg,2022, 57(2):106-129. doi:10.3760/cma.j.cn115330-20211228-00828.
[8]	Tamasauskiene L, Gasiuniene E, Sitkauskiene B. Translation,adaption and validation of the total nasal symptom score (TNSS) for Lithuanian population[J]. Health Qual Life Outcomes, 2021, 19:54. doi:10.1186/s12955-020-01659-8.
[9]	王阳阳, 黄霄云, 冯茂胜. 柴胡疏肝散对糖尿病周围神经病变大鼠瞬时受体电位香草酸亚型1/降钙素基因相关肽通路及坐骨神经电生理变化的影响[J]. 安徽医药, 2023, 27(7):1312-1317,1485.
	Wang Y Y, Huang X Y, Feng M S. Effects of Chaihu Shugan powder on TRPV1/CGRP pathway and electrophysiological changes of sciatic nerve in DPN rats[J]. Anhui Med Pharm J, 2023, 27(7):1312-1317,1485. doi:10.3969/j.issn.1009-6469.2023.07.009.
[10]	Xu J, Ghadiri M, Svolos M, et al. Investigating potential TRPV1 positive feedback to explain TRPV1 upregulation in airway disease states[J]. Drug Dev Ind Pharm, 2021, 47(12):1924-1934. doi:10.1080/03639045.2022.2070759.
[11]	Wang Y, Qi X, Li H, et al. Inhibition of TRPV1 attenuates innate nasal epithelial responses via NF-κB signaling pathway in allergic rhinitis[J]. Int Immunopharmacol, 2025, 158(1):114807. doi:10.1016/j.intimp.2025.114807.
[12]	Alenmyr L, Högestätt E D, Zygmunt P M, et al. TRPV1-mediated itch in seasonal allergic rhinitis[J]. Allergy, 2009, 64(5):807-810. doi:10.1111/j.1398-9995.2009.01937.x.
[13]	黄存军, 刘韵, 欧秋娟, 等. DNMT1通过SOCS1影响高糖诱导足细胞凋亡和炎性细胞因子释放[J]. 免疫学杂志, 2024, 40(3):265-271.
	Huang C J, Liu Y, Ou Q J, et al. Effects of DNMT1 on high glucose-induced apoptosis and inflammatory cytokine release in podocytes via SOCS1[J]. Immunol J, 2024, 40(3):265-271. doi:10.13431/j.cnki.immunol.j.20240034.
[14]	邹浩冬, 杨飞, 张莞嫣, 等. DNMT1在口腔鳞状细胞癌中的表达及作用机制研究[J]. 川北医学院学报, 2024, 39(1):12-17.
	Zou H D, Yang F, Zhang W Y, et al. Expression and mechanism of DNMT1 in oral squamous cell carcinoma[J]. Journal of North Sichuan Medical College, 2024, 39(1):12-17. doi:10.3969/j.issn.1005-3697.2024.01.003.
[15]	Zou P, Li J G, Li J, et al. Inhibition of DNA methyltransferase DNMT1 reverses Th2 response polarisation and alleviates allergic rhinitis[J]. Clin Exp Pharmacol Physiol, 2025, 52(2):e70015. doi:10.1111/1440-1681.70015.
[16]	Elahi M, Ebrahim Soltani Z, Afrooghe A, et al. Sex dimorphism in pain threshold and neuroinflammatory response:the protective effect of female sexual hormones on behavior and seizures in an allergic rhinitis model[J]. J Neuroimmune Pharmacol, 2024, 19:16. doi:10.1007/s11481-024-10114-0.
[17]	Li L J, Pang W J, Xu L Z, et al. Inhibition of DNMT1 attenuates experimental food allergy[J]. Mol Immunol, 2024, 173:71-79. doi:10.1016/j.molimm.2024.07.009.
[18]	Hohlstein P, Brozat J F, Schuler J, et al. Secreted frizzled related protein 5(SFRP5) serum levels are decreased in critical illness and sepsis and are associated with short-term mortality[J]. Biomedicines, 2023, 11(2):313. doi:10.3390/biomedicines11020313.
[19]	Shi Z, Xu M, Chen X, et al. The regulatory role of SFRP5/WNT5A axis in allergic rhinitis through inhibiting JNK pathway activation and lowering mucin generation in human nasal epithelial cells[J]. Exp Mol Pathol, 2021, 118:104591. doi:10.1016/j.yexmp.2020.104591.
[20]	Sun M, Wang W, Min L, et al. Secreted frizzled-related protein 5(SFRP5) protects ATDC5 cells against LPS-induced inflammation and apoptosis via inhibiting Wnt5a/JNK pathway[J]. J Orthop Surg Res, 2021, 16:129. doi:10.1186/s13018-021-02260-5.
[21]	崔令运, 刘波, 王晓伦. 外周血hs-CRP、OPN、NO、PLR联合检查对过敏性鼻炎患者病情严重程度的预测价值[J]. 中国卫生检验杂志, 2023, 33(3):353-356,371.
	Cui L Y, Liu B, Wang X L. Predictive value of combined examination of high-sensitivity C-reactive protein,osteopontin,nitric oxide and platelet/lymphocyte ratio in peripheral blood of patients with allergic rhinitis[J]. Chin J Health Lab Technol, 2023, 33(3):353-356,371.

组别	n		年龄/岁		性别（男/女）		病程/年
轻中症AR组	75		35.52±4.26		34/41		4.54±1.31
重症AR组	45		34.33±4.31		21/24		5.03±1.82
t或χ2			1.475		0.020		1.709
组别	BMI/（kg/m²）		吸烟史		合并哮喘		家族过敏史
轻中症AR组	22.83±1.25		15（20.00）		11（14.67）		28（37.33）
重症AR组	22.41±1.27		10（22.22）		19（42.22）		24（53.33）
t或χ²	1.771		0.084		11.390^＊＊		2.932
组别		接触粉尘史		IgE/（IU/mL）		TNSS评分/分
轻中症AR组		4（5.33）		235.65±68.40		5.84±1.02
重症AR组		7（15.56）		512.30±102.50		9.64±1.24
t或χ²		3.530		17.725^＊＊		18.202^＊＊

组别	n		年龄/岁		性别（男/女）		病程/年
轻中症AR组	75		35.52±4.26		34/41		4.54±1.31
重症AR组	45		34.33±4.31		21/24		5.03±1.82
t或χ2			1.475		0.020		1.709
组别	BMI/（kg/m²）		吸烟史		合并哮喘		家族过敏史
轻中症AR组	22.83±1.25		15（20.00）		11（14.67）		28（37.33）
重症AR组	22.41±1.27		10（22.22）		19（42.22）		24（53.33）
t或χ²	1.771		0.084		11.390^＊＊		2.932
组别		接触粉尘史		IgE/（IU/mL）		TNSS评分/分
轻中症AR组		4（5.33）		235.65±68.40		5.84±1.02
重症AR组		7（15.56）		512.30±102.50		9.64±1.24
t或χ²		3.530		17.725^＊＊		18.202^＊＊

组别	n	TRPV1/（μg/L）	DNMT1/（μg/L）	SFRP5/（ng/L）
轻中症AR组	75	5.93±1.25	6.25±1.36	20.78±4.63
重症AR组	45	7.14±1.07	8.09±1.28	15.11±4.41
t		5.410^＊＊	7.333^＊＊	6.610^＊＊

组别	n	TRPV1/（μg/L）	DNMT1/（μg/L）	SFRP5/（ng/L）
轻中症AR组	75	5.93±1.25	6.25±1.36	20.78±4.63
重症AR组	45	7.14±1.07	8.09±1.28	15.11±4.41
t		5.410^＊＊	7.333^＊＊	6.610^＊＊

变量	β	SE	Wald χ²	P	OR	OR 95%CI
TRPV1	0.612	0.185	10.941	0.001	1.844	1.283~2.650
DNMT1	0.857	0.213	16.187	<0.001	2.356	1.552~3.577
SFRP5	-0.145	0.041	12.512	<0.001	0.865	0.798~0.937
常数项	0.758	1.052	0.519	0.471	2.133