蒙药盲嘎日热敷疗法治疗神经根型颈椎病的临床疗效及药效物质基础:一项随机对照试验和血清药理化学研究

Clinical efficacy and pharmacological basis of Mongolian medicine Manggari hot compress therapy for cervical spondylotic radiculopathy: a randomized controlled trial and serum pharmacochemistry study

  • 摘要:
    目的 本研究旨在系统评价蒙药盲嘎日外用敷剂热敷疗法(以下简称盲嘎日热敷疗法)治疗神经根型颈椎病(CSR)的临床疗效,并探索该方中可能的药效物质基础,为蒙医学在CSR治疗中的临床应用提供依据。
    方法 本临床试验采用随机对照、开放标签、结局评价盲法设计,选取2024年7月1日至2025年10月31日期间就诊于锡林郭勒盟蒙医医院传统疗术科门诊的CSR患者。患者随机分为3组:口服对照组(甲钴胺片联合颈椎电牵引)、试验组(盲嘎日外用热敷)和贴敷对照组(氟比洛芬凝胶贴敷),干预周期为两周。记录患者治疗前后蒙医证候(MMS)评分、视觉模拟评分法(VAS)评分、颈痛量表(NPQ)评分以及舌象;采用酶联免疫吸附试验(ELISA)检测患者治疗前后血清炎症指标肿瘤坏死因子 (TNF)-α、白细胞介素 (IL)-6、IL-1β及氧化应激指标丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-Px)活性;最后对总体疗效进行评定。治疗结束1个月后随访,再次记录患者MMS、VAS、NPQ评分。在药效物质基础方面,采用超高效液相色谱-四极杆静电场轨道阱质谱(UHPLC-QE-MS)技术,在正负离子模式下对盲嘎日的入血成分进行分析,并通过分子对接验证核心活性化合物与靶蛋白之间的靶向关系。
    结果 本研究最终纳入90例CSR患者,三组患者的基线资料无统计学差异(P > 0.05)。(1)症状评分:三组患者治疗后MMS、VAS、NPQ评分较基线均明显下降(P < 0.001);随访时,试验组的MMS、VAS、NPQ评分与治疗结束时相比无显著差异(P > 0.05)。试验组较口服对照组和贴敷对照组在MMS、VAS、NPQ评分下降显著(P < 0.001),随访时差异仍显著(P < 0.001)。(2)炎症及氧化应激指标:三组患者治疗后血清中TNF-α、IL-6、IL-1β含量及MDA活性均较基线明显下降(P < 0.05),SOD含量、GSH-Px活性均较基线明显上升(P < 0.05)。治疗后试验组较口服对照组和贴敷对照组可显著降低TNF-α、IL-6及IL-1β含量,同时降低MDA活性,升高SOD含量及GSH-Px活性(P < 0.05)。(3)总体疗效:试验组总有效率为93.33%,口服对照组为86.66%,贴敷对照组为83.33%。(4)药效物质分析:盲嘎日的入血成分共筛选出152种化合物,其中核心化合物4-羟基香豆素、N-甲基蒽酸、染料木素及人参皂苷-Rk1与关键靶蛋白TNF-α、IL-1β之间的结合能范围为 − 4.7 至− 7.1 kcal/mol,其中大多数结合能低于 − 5.0 kcal/mol,提示其总体具有较好的结合亲和力。
    结论 蒙医热敷疗法通过其热效应和活性药物成分盲嘎日的共同作用,有效调节炎症和氧化应激反应,抑制颈神经根炎症,缓解神经根性疼痛,从而在CSR中取得疗效,改善患者临床症状、疼痛程度及颈椎功能障碍。

     

    Abstract:
    Objective To systematically evaluate the clinical efficacy of topical preparations of Mongolian medicine Manggari hot compress therapy (hereafter referred to as Manggari hot compress therapy) in treating cervical spondylotic radiculopathy (CSR) and explore the possible pharmacological material basis in the formula, providing evidence for the clinical application of Mongolian medicine in the treatment of CSR.
    Methods The clinical trial employed a randomized, controlled, open-label, and outcome-assessor-blinded design. The CSR patients who were treated at the Department of Traditional Therapeutics Outpatient Clinic, Xilinguole Meng Mongolian General Hospital between July 1, 2024 and August 31, 2025, were enrolled. They were randomly assigned to three groups: an oral control group (administration of oral administration of mecobalamin tablets combined with cervical electric traction), an experimental group (Manggari external hot compress), and a patch control group (flurbiprofen gel plaster). The intervention lasted two weeks. Before and after treatment, the following subjective indicators were recorded: Mongolian Medicine Syndrome (MMS) score, Visual Analog Scale (VAS) score, Northwick Park Neck Pain Questionnaire (NPQ) score, and tongue morphology. Serum levels of inflammatory markers tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β) and oxidative stress markers malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-Px) activity were measured using enzyme-linked immunosorbent assay (ELISA). Overall therapeutic efficacy was evaluated. One month after treatment completion, a follow-up assessment was conducted, and the MMS, VAS, and NPQ scores were recorded again for all patients. For the pharmacological substance exploration, ultra-high-performance liquid chromatography-Q-exactive orbitrap-mass (UHPLC-QE-MS) was employed to analyze blood-absorbed prototype components of Manggari, under both positive and negative ion modes. The targeting relationship between the core active compounds and the target protein was validated using molecular docking.
    Results This study ultimately included 90 patients with CSR for analysis. Baseline characteristics showed no statistically significant differences among the three groups (P > 0.05). (i) Symptom scores. After treatment, the MMS, VAS, and NPQ scores decreased significantly from baseline in all three groups (P < 0.001). At follow-up, there was no significant difference in MMS, VAS, and NPQ scores of the experimental group compared with those at the end of the treatment (P > 0.05). After treatment, the experimental group showed significantly greater reductions in MMS, VAS, and NPQ scores than oral control and patch control groups (P < 0.001). At follow-up, these differences remained significant (P < 0.001). (ii) Inflammatory and oxidative stress markers. After treatment, serum levels of TNF-α, IL-6, and IL-1β, and MDA activity decreased significantly from baseline in all three groups (P < 0.001), and SOD content and GSH-Px activity increased significantly from baseline (P < 0.05). After treatment, the experimental group had significantly lower serum levels of TNF-α, IL-6, and IL-1β than oral and patch control groups. Additionally, it exhibited lower MDA activity and higher SOD content and GSH-Px activity compared with the two control groups. (P < 0.05). (iii) Overall efficacy. The total effective rate was 93.33% in the experimental group, 86.66% in the oral control group, and 83.33% in the patch control group. (iv) Pharmacological substance analysis. A total of 152 compounds were identified in the blood-absorbed components of Manggari. Among them, the core compounds—4-hydroxycoumarin, N-methylanthranilic acid, genistein, and ginsenoside-Rk1—showed binding energies to the key target proteins TNF-α and IL-1β range from − 4.7 to − 7.1 kcal/mol, with the majority of the binding energies being below − 5.0 kcal/mol, suggesting that it generally has a good binding affinity.
    Conclusion Mongolian medicine hot compress therapy effectively modulates inflammatory and oxidative stress responses through the combined action of its thermal effects and active pharmaceutical ingredients Manggari. It inhibits cervical nerve root inflammation and alleviates radicular pain, improving clinical symptoms, reducing pain severity, and alleviating neck functional disability.

     

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