老年带状疱疹急性期METTL3及Gal-3表达水平对带状疱疹后遗神经痛的预测价值

doi:10.3969/j.issn.1003-9198.2024.04.006

摘要/Abstract

摘要： 目的研究老年带状疱疹(herpes zoster, HZ)病人急性期外周血甲基转移酶样因子3(METTL3)及半乳糖凝集素3(Gal-3)的表达情况,并探讨其预测带状疱疹后遗神经痛(postherpetic neuralgia, PHN)的价值。方法选取我院2019年1月至2022年1月诊治的190例老年HZ病人为研究对象,另选取50例健康体检的老年人为对照组,检测受试对象外周血METTL3 mRNA及血清Gal-3蛋白表达水平并进行比较分析。根据HZ病人是否发生PHN分为PHN组(n=44)和无PHN组(NPHN组)(n=146),采用Logistic回归分析PHN的相关因素,绘制ROC曲线评估METTL3 mRNA及Gal-3蛋白表达水平对PHN的预测价值。结果 HZ病人外周血单个核细胞(peripheral blood mononuclear cells, PBMC)中METTL3 mRNA相对表达量低于对照组,血清Gal-3蛋白水平高于对照组,差异具有统计学意义(均P<0.05)。老年PHN病人METTL3 mRNA表达水平与VAS评分呈负相关(r=-0.612,P<0.05),血清Gal-3蛋白水平与VAS评分呈正相关(r=0.604,P<0.05)。Logistic回归分析结果显示,病程(OR=1.756,95%CI:1.253~2.460)、Gal-3蛋白(OR=1.318,95%CI:1.025~1.693)是影响老年PHN发生的风险因素,METTL3 mRNA(OR=0.742,95%CI:0.581~0.948)是保护因素。METTL3 mRNA及Gal-3蛋白联合预测老年PHN的曲线下面积为0.924(95%CI:0.843~0.958),高于单项检测0.812(0.774~0.861)、0.859(0.811~0.897),差异具有统计学意义(Z=4.312、3.363,均P<0.05)。结论老年急性期HZ病人外周血PBMC中METTL3 mRNA表达降低,血清Gal-3蛋白表达升高,两者联合对老年PHN的发生具有较高的预测价值。

关键词: 老年人, 带状疱疹, 带状疱疹后遗神经痛, 甲基转移酶样因子3, 半乳糖凝集素3, 预测价值

Abstract: Objective To study the expression of methyltransferase-like factor 3 (METTL3) and galectin 3 (Gal-3) in peripheral blood of elderly patients with acute phase of herpes zoster (HZ) and the predictive value for postherpetic neuralgia (PHN). Methods A total of 190 elderly patients with acute HZ treated in our hospital from January 2019 to January 2022 were enrolled in this study. They were divided into PHN group (n=44) and NPHN group (n=146) according to whether the patients presented with PHN. Another 50 healthy subjects who underwent physical examination were enrolled as control group. Fluorescence quantitative PCR and enzyme linked immunosorbent assay were used to detect the expression of METTL3 mRNA in peripheral blood mononuclear cells (PBMC) and serum level of Gal-3 protein, respectively. Logistic regression analysis was used to analyze the influencing factors of PHN in the elderly patients with HZ, and ROC curve was used to investigate the predicting value of the influencing factors. Results The relative expression of METTL3 mRNA in PBMC was significantly lower and the serum level of Gal-3 protein was significantly higher in the patients with HZ than that in control group (P<0.05). The level of METTL3 mRNA was negatively correlated with visual analogue score (VAS), while the serum level of Gal-3 protein was positively correlated with VAS (r=-0.612, 0.604, P<0.05) in the elderly patients with PHN. The course of disease (OR=1.756, 95%CI:1.253-2.460) and the level of Gal-3 protein (OR=1.318, 95%CI:1.025-1.693) were risk factors of the occurrence of PHN in the elderly, while the level of METTL3 mRNA (OR=0.742, 95%CI:0.581-0.948) was a protective factor. The area under ROC curve of METTL3 mRNA combined with Gal-3 protein for predicting PHN was 0.924 (0.843-0.958), compared with 0.812 (0.774-0.861), 0.859 (0.811-0.897) of the two parameters alone (Z=4.312, 3.363, P<0.05). Conclusions The combination of METTL3 mRNA expression in PBMC and serum Gal-3 protein expression has high predictive value for the occurrence of PHN in the elderly patients with acute HZ.

Key words: aged, herpes zoster, postherpetic neuralgia, methyltransferase like factor 3, galactose agglutinin 3, forecasting value

中图分类号:

R 752.12

张玉林, 方启帆, 赵永明, 吴泽宇, 杨颖. 老年带状疱疹急性期METTL3及Gal-3表达水平对带状疱疹后遗神经痛的预测价值[J]. 实用老年医学, 2024, 38(4): 348-352.

ZHANG Yulin, FANG Qifan, ZHAO Yongming, WU Zeyu, YANG Ying. Value of METTL3 and galectin 3 in peripheral blood in predicting postherpetic neuralgia in elderly patients with acute phase of herpes zosfer[J]. Practical Geriatrics, 2024, 38(4): 348-352.

参考文献

[1] PATIL A, GOLDUST M, WOLLINA U. Herpes zoster: a review of clinical manifestations and management[J]. Viruses, 2022, 14(2):457-466.
[2] COHEN E J. Commentary on herpes zoster and postherpetic neuralgia[J]. Clin Infect Dis, 2021, 73(9): e3218-e3219.
[3] ZENG C, HUANG W, LI Y, et al. Roles of METTL3 in cancer: mechanisms and therapeutic targeting[J]. J Hematol Oncol, 2020, 13(1): 117-125.
[4] PAN Z, ZHANG Q, LIU X, et al. Methyltransferase-like 3 contributes to inflammatory pain by targeting TET1 in YTHDF2-dependent manner[J]. Pain, 2021, 162(7):1960-1976.
[5] SOARES L C, AL-DALAHMAH O, HILLIS J, et al. Novel Galectin-3 roles in neurogenesis, inflammation and neurological diseases[J]. Cells, 2021, 10(11):1247-1256.
[6] KOYANAGI M, IMAI S, MATSUMOTO M, et al. Pronociceptive roles of schwann cell-derived galectin-3 in taxane-induced peripheral neuropathy[J]. Cancer Res, 2021, 81(8):2207-2219.
[7] 中国医师协会皮肤科医师分会带状疱疹专家共识工作组. 带状疱疹中国专家共识[J]. 中华皮肤科杂志, 2018, 51(6): 403-408.
[8] DUBINSKY R M, KABBANI H, EL-CHAMI Z, et al. Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology[J]. Neurology, 2004, 63(6): 959-965.
[9] YANG F, YU S, FAN B, et al. The epidemiology of herpes zoster and postherpetic neuralgia in China: results from a cross-sectional study[J]. Pain Ther, 2019, 8(2): 249-259.
[10]皇甫佳欣, 沈德新. 带状疱疹后遗神经痛的中西医治疗进展[J]. 中国医药导报, 2020, 17(12): 65-68.
[11]WARNER B E, GOINS W F, KRAMER P R, et al. A guide to preclinical models of zoster-associated pain and postherpetic neuralgia[J]. Curr Top Microbiol Immunol, 2022. 43(8): 189-221.
[12]LI Y, GUO X, SUN L, et al. N⁶-methyl adenosine demethylase FTO contributes to neuropathic pain by stabilizing G9a expression in primary sensory neurons[J]. Adv Sci: Weinh, 2020, 7(13): 1902-1914.
[13]DU K, ZHANG L, LEE T, et al. m⁶A RNA methylation controls neural development and is involved in human diseases[J]. Mol Neurobiol, 2019, 56(3): 1596-1606.
[14]WANG W, LI Y, FAN J, et al. MiR-365-3p is a negative regulator in IL-17-mediated asthmatic inflammation[J]. Front Immunol, 2022, 13(9): 9537-9544.
[15]ZHANG L, ZHAO X, WANG J, et al. METTL3 suppresses neuropathic pain via modulating N6-methyladenosine-dependent primary miR-150 processing[J]. Cell Death Discov, 2022, 8(1): 80-87.
[16]BURGUILLOS M A, SVENSSON M, SCHULTE T, et al. Microglia-secreted galectin-3 acts as a toll-like receptor 4 ligand and contributes to microglial activation[J]. Cell Rep, 2015, 10(9): 1626-1638.
[17]TAKASAKI I, TANIGUCHI K, KOMATSU F, et al. Contribution of spinal galectin-3 to acute herpetic allodynia in mice[J]. Pain, 2012, 153(3): 585-592.
[18]LI J, GUO Y, CHEN Y Y, et al. miR-124-3p increases in high glucose induced osteocyte-derived exosomes and regulates galectin-3 expression: a possible mechanism in bone remodeling alteration in diabetic periodontitis[J]. FASEB J, 2020, 34(11):14234-14249.