Gao Zijun, Gong Ling, Li Lu, Song Lei, Xiao JianBo, Zhuang Jian, Wang Fang
From the Key Laboratory of Education Ministry for Modern Design Rotor-Bearing System, Xi'an Jiaotong University, Xi'an 710049, China; School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an 710049, China (ZG, JZ), Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi, China (LL, LS, JX, FW), College of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China (LG).
Eur J Anaesthesiol. 2025 Sep 18. doi: 10.1097/EJA.0000000000002256.
Activation of mast cells and systemic histamine release are major side effects of intravenously administered neuromuscular blocking agents (NMBAs). Mas-related G protein-coupled receptor-X2 (MRGPRX2) plays a key role in mediating anaphylactoid reactions.
To explore the mechanism of acute anaphylactic shock induced by muscle relaxants through the typical shock cases.
Case report and case control study.
A 68-year-old male patient (80 kg) underwent surgical treatment in September 2023 and developed anaphylactic shock during anaesthesia induction.
A trial was conducted to evaluate the patient who experienced anaphylactic shock during the peri-operative period in comparison to control patients. The levels of MRGPRX2 and total immunoglobulin E (IgE) were measured in patient plasma, along with allergic mediators such as histamine and tryptase. Mast cell activation assay was performed to assess degranulation effectiveness by measuring β-hexosaminidase, histamine release, and calcium influx. Additionally, mast cell activation by peri-operative drugs was investigated. Local inflammatory experiments were conducted in a mouse model to evaluate rocuronium bromide-induced allergic reactions. Finally, MRGPRB2-CKO mice and siRNA silencing were used to elucidate the mechanism of rocuronium-induced anaphylactic shock.
Plasma analysis of the patient experiencing anaphylaxis revealed normal total IgE levels (38.4 IU ml-1) but significantly elevated histamine concentration (53.78 ng ml-1). The MRGPRX2 concentration (52.22 ng ml-1) in this patient was markedly higher than the negative control group (16.40 ng ml-1). Serum-activated mast cell assays demonstrated that the anaphylaxis patient's plasma induced a significant release of β-hexosaminidase, calcium, and histamine from mast cells (significantly higher than the histamine levels naturally present in the plasma). Drug-activated mast cell experiments confirmed that rocuronium bromide triggered dose-dependent mast cell activation, leading to MCP-1, histamine, and calcium release. Local paw oedema experiments in mice further validated that rocuronium bromide induced local allergic reactions. Using MRGPRB2-CKO mice and siRNA silencing, we determined that rocuronium bromide-induced anaphylactic shock was mediated through MRGPRX2 activation, resulting in mast cell degranulation.
This study highlights the critical role of MRGPRX2 in rocuronium bromide-induced anaphylactic shock. In vitro diagnosis of MRGPRX2 levels may provide new criteria for reducing intra-operative risks.
The clinical trial was registered at the China Clinical Trial Registration Center (Registration Number: ChiCTR2300077364).
肥大细胞的激活和全身组胺释放是静脉注射神经肌肉阻滞剂（NMBAs）的主要副作用。与马斯相关的G蛋白偶联受体X2（MRGPRX2）在介导类过敏反应中起关键作用。
通过典型休克病例探讨肌肉松弛剂诱发急性过敏性休克的机制。
病例报告和病例对照研究。
一名68岁男性患者（80千克）于2023年9月接受手术治疗，在麻醉诱导期间发生过敏性休克。
进行一项试验，将围手术期发生过敏性休克的患者与对照患者进行比较。检测患者血浆中MRGPRX2和总免疫球蛋白E（IgE）水平，以及组胺和类胰蛋白酶等过敏介质。进行肥大细胞激活试验，通过测量β-己糖胺酶、组胺释放和钙内流来评估脱颗粒效果。此外，研究围手术期药物对肥大细胞的激活作用。在小鼠模型中进行局部炎症实验，以评估罗库溴铵诱发的过敏反应。最后，使用MRGPRB2基因敲除小鼠和小干扰RNA沉默技术来阐明罗库溴铵诱发过敏性休克的机制。
对发生过敏反应的患者进行血浆分析，结果显示总IgE水平正常（38.4IU/ml），但组胺浓度显著升高（53.78ng/ml）。该患者的MRGPRX2浓度（52.22ng/ml）明显高于阴性对照组（16.40ng/ml）。血清激活的肥大细胞试验表明，过敏反应患者的血浆可诱导肥大细胞显著释放β-己糖胺酶、钙和组胺（显著高于血浆中天然存在的组胺水平）。药物激活的肥大细胞实验证实，罗库溴铵可触发剂量依赖性的肥大细胞激活，导致单核细胞趋化蛋白-1、组胺和钙释放。小鼠局部爪肿胀实验进一步验证了罗库溴铵可诱发局部过敏反应。使用MRGPRB2基因敲除小鼠和小干扰RNA沉默技术，我们确定罗库溴铵诱发的过敏性休克是通过MRGPRX2激活介导的，导致肥大细胞脱颗粒。
本研究强调了MRGPRX2在罗库溴铵诱发的过敏性休克中的关键作用。体外诊断MRGPRX2水平可能为降低术中风险提供新的标准。
该临床试验在中国临床试验注册中心注册（注册号：ChiCTR2300077364）。
