中华皮肤科杂志 ›› 2025, Vol. 58 ›› Issue (2): 161-166.doi: 10.35541/cjd.20230699

• 论著 • 上一篇    下一篇

纳洛酮改善慢性砷暴露相关瘙痒人群健康相关生活质量的效果：一项随机、双盲、安慰剂对照试验

黄晓燕1，2    粟娟1    陈明亮1    陈翔1    肖易1    沈敏学1，3   

  1. 1中南大学湘雅医院皮肤病医院，长沙  410008；2中南大学湘雅医院病理科，长沙  410008；3中南大学湘雅公共卫生学院社会医学与卫生事业管理学系，长沙  410008
  • 收稿日期:2023-11-30 修回日期:2024-09-13 发布日期:2025-02-07
  • 通讯作者: 沈敏学 E-mail:shenmx1988@csu.edu.cn
  • 基金资助:
    国家科技基础性工作专项（2015FY111100）；湖南省自然科学基金（2023JJ40921）；湖南省科技创新计划（2022RC1014）

Efficacy of naloxone in improving health-related quality of life in patients with chronic arsenic exposure-related pruritus: a randomized, double-blind, placebo-controlled trial

Huang Xiaoyan1,2, Su Juan1, Chen Mingliang1, Chen Xiang1, Xiao Yi1, Shen Minxue1,3   

  1. 1Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, China; 2Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China; 3Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha 410008, China
  • Received:2023-11-30 Revised:2024-09-13 Published:2025-02-07
  • Contact: Shen Minxue E-mail:shenmx1988@csu.edu.cn
  • Supported by:
    National Project on Basic Work in Science and Technology （2015FY111100）; Natural Science Foundation of Hunan Province, China  （2023JJ40921）; Science and Technology Innovation Program of Hunan Province  （2022RC1014）
    Trial registration: ClinicalTrials.gov （NCT03751111）

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摘要： 【摘要】 目的 明确纳洛酮改善慢性砷暴露相关瘙痒人群健康相关生活质量的效果，并研究砷代谢及内啡肽受体相关基因多态性的修饰效应。方法 本研究为随机、双盲、对照试验，于2019年1 - 3月在湖南省常德市某砷暴露人群中招募符合条件的中重度慢性瘙痒患者，随机分配至干预组和对照组，舌下含服纳洛酮或安慰剂（0.4 mg/d），连续7 d。在给药前和给药第7天对患者进行重复测量，主要结局为皮肤病生活质量指数（DLQI），次要结局为抑郁症状、焦虑症状和睡眠质量。使用连接酶检测反应分型技术进行三价砷甲基转移酶基因和3个阿片类受体基因的分型。正态分布的连续变量采用t检验，偏态分布的连续变量采用非参数检验，计数资料采用卡方检验进行组间比较。采用线性回归分析不同药物干预对结局指标的影响，采用广义线性模型分析人口学信息及各基因型与治疗分组对DLQI变化值的交互作用。结果 共纳入126例慢性砷暴露相关瘙痒患者，男73例，女53例，随机分配至对照组64例和干预组62例，年龄分别为（60.0 ± 9.1）岁和（58.4 ± 8.6）岁。两组患者的年龄、性别、收入、受教育程度及发砷浓度的差异无统计学意义（均P > 0.05）。干预后，干预组患者DLQI下降变化值大于对照组，且差异具有统计学意义（-8.79 ± 6.84比-5.19 ± 8.10； P = 0.008），但抑郁症状、焦虑症状及睡眠质量的变化值差异无统计学意义（均P > 0.05）。线性回归分析示纳洛酮显著影响DLQI变化，粗回归系数为-3.60（95% CI：-6.25，-0.96；P = 0.008）。分层分析显示κ阿片类受体基因rs1051660野生型（CC）患者的治疗应答显著优于突变型（CA），仅rs1051660基因型和药物对DLQI变化的影响有交互作用（P = ?0.014）。结论 纳洛酮可有效改善慢性砷暴露相关瘙痒患者健康相关生活质量，κ阿片类受体基因单核苷酸多态性与治疗应答有关。

关键词: 砷中毒, 瘙痒症, 纳洛酮, 生活质量, 环境暴露, 临床试验, 砷暴露

Abstract: 【Abstract】 Objective To investigate the efficacy of naloxone in improving health-related quality of life in patients with chronic arsenic exposure-related pruritus, and to explore the modification effect of gene polymorphisms associated with arsenic metabolism and endorphin receptors. Methods A randomized, double-blind, placebo-controlled trial was conducted between January and March 2019 in Changde City, Hunan Province, China. Eligible patients with moderate to severe chronic pruritus under arsenic exposure were recruited, and randomly assigned to the naloxone group and the control group to receive sublingual naloxone and placebo （0.4 mg/d） respectively for 7 consecutive days. Outcomes were assessed before treatment and on day 7 after treatment, including the primary outcome （the dermatology life quality index ［DLQI］） and secondary outcomes （depression symptoms, anxiety symptoms, and quality of sleep）. Genotyping of the arsenic （+3 oxidation state） methyltransferase and 3 opioid receptor genes was performed using ligase detection reaction. Data analysis was performed using t test for normally distributed continuous variables, non-parametric tests for skewed continuous variables, and chi-square test for categorical data. Linear regression analysis was carried out to evaluate the effect of naloxone on outcome measures, while the interactive effect of demographic factors, genotypes and treatment methods on changes in DLQI were assessed by the generalized linear model. Results A total of 126 patients with chronic arsenic exposure-related pruritus were enrolled, including 73 males and 53 females. They were randomly divided into the control group （64 cases） and the naloxone group （62 cases）, with the ages being 60.0 ± 9.1 years and 58.4 ± 8.6 years, respectively. There were no significant differences between the two groups in terms of age, gender, income, education levels, or hair arsenic concentrations （all P > 0.05）. After treatment, the decrease in DLQI scores was significantly higher in the naloxone group than in the control group （-8.79 ± 6.84 vs. -5.19 ± 8.10; P = 0.008）. However, there were no significant changes in depression symptoms, anxiety symptoms, or quality of sleep between the naloxone group and control group （all P > 0.05）. Linear regression analysis showed that naloxone significantly affected DLQI with a crude regression coefficient of -3.60 （95% CI: -6.25, -0.96; P = 0.008）. Stratification analysis revealed that patients with the κ-opioid receptor gene rs1051660 （wild-type, CC） responded better to the treatment than those with the mutated genotype （CA）, and there was a significant interaction between the rs1051660 genotype and therapeutic drugs in relation to DLQI changes （P = 0.014）. Conclusion Naloxone can effectively improve health-related quality of life in patients with chronic arsenic exposure-related pruritus, and its efficacy is modified by the gene polymorphism of the κ-opioid receptors.

Key words: Arsenic poisoning, Pruritus, Naloxone, Quality of life, Environmental exposure, Clinical trial, Arsenic exposure

引用本文

黄晓燕 粟娟 陈明亮 陈翔 肖易 沈敏学. 纳洛酮改善慢性砷暴露相关瘙痒人群健康相关生活质量的效果：一项随机、双盲、安慰剂对照试验[J]. 中华皮肤科杂志, 2025,58(2):161-166. doi:10.35541/cjd.20230699

Huang Xiaoyan, Su Juan, Chen Mingliang, Chen Xiang, Xiao Yi, Shen Minxue, . Efficacy of naloxone in improving health-related quality of life in patients with chronic arsenic exposure-related pruritus: a randomized, double-blind, placebo-controlled trial[J]. Chinese Journal of Dermatology, 2025, 58(2): 161-166.doi:10.35541/cjd.20230699