Mrgprb2 基因在鱼腥草注射液引起的过敏样反应中发挥作用。
Mrgprb2 gene plays a role in the anaphylactoid reactions induced by Houttuynia cordata injection.
机构信息
School of Pharmacy, Jiangsu University, Zhenjiang, 212000, China.
School of Pharmacy, Jiangsu University, Zhenjiang, 212000, China.
出版信息
J Ethnopharmacol. 2022 May 10;289:115053. doi: 10.1016/j.jep.2022.115053. Epub 2022 Jan 29.
ETHNOPHARMACOLOGICAL RELEVANCE
Houttuynia cordata Thunb., a plant belonging to the family of Saururaceae, has been used as a traditional Chinese medicine for more than 1500 years. Because of its various pharmacological activities, it was widely used as antipyretic, detoxification, anti-inflammatory drugs. Houttuynia cordata (HC) injection was prepared using contemporary methods to extract effective components from H. cordata Thunb. However, the adverse event reports of HC injection are accumulating remarkably with the HC injection clinical applications increased. Previous studies demonstrated that the major side effects of HC injection were anaphylactoid reactions. Our work might shed the light on the role of Mas-related G-protein coupled receptor-X2 (MRGPRX2) in modulating drug-induced anaphylactoid reactions.
AIM OF THE STUDY
We aimed to investigate the role of the mouse Mas-related G-protein coupled receptor B2 (Mrgprb2) (the orthologous gene of human MRGPRX2) in anaphylactoid reactions induced by HC injection.
MATERIALS AND METHODS
Mrgprb2 related anaphylactoid reactions induced by HC injection were investigated by histamine/β-hexosaminidase releasing, mast cell degranulation, and hind paw swelling assays by using a Mrgprb2 knockout mouse model. Furthermore, the transcriptomic profiles of the anaphylactoid reaction induced by HC injection was analyzed by RNA sequencing.
RESULTS
Mice without Mrgprb2 exhibited significantly decreasing in mast cell degranulation, serum histamine release, and hind paw swelling degrees. The RNA sequencing results indicated that Mrgprb2 could play a pivotal role in HC injection induced anaphylactoid reaction mediated by mTOR/AMPK pathway. Intriguingly, our results showed that Mrgprb2 might involve in Compound 48/80 induced anaphylactoid reactions mediated by Reelin/E-cadherin axis, which suggested different roles of Mrgprb2 in anaphylactoid reactions induced by HC injection and C48/80.
CONCLUSION
Our studies reported effects and underlying mechanisms of Mrgprb2 in the anaphylactoid reaction induced by HC injection.
ethnopharmacological 相关性：鱼腥草，属于三白草科的一种植物，作为一种传统的中药已经使用了超过 1500 年。由于其具有多种药理活性，它被广泛用作解热、解毒、抗炎药物。鱼腥草注射液是采用现代方法从鱼腥草中提取有效成分制备而成的。然而，随着鱼腥草注射液临床应用的增加，其不良反应报告显著增加。以前的研究表明，鱼腥草注射液的主要副作用是类过敏反应。我们的工作可能揭示了 Mas 相关 G 蛋白偶联受体-X2（MRGPRX2）在调节药物引起的类过敏反应中的作用。
研究目的
本研究旨在探讨小鼠 Mas 相关 G 蛋白偶联受体 B2（Mrgprb2）（人类 MRGPRX2 的同源基因）在鱼腥草注射液引起的类过敏反应中的作用。
材料和方法
通过组胺/β-己糖胺酶释放、肥大细胞脱颗粒和后爪肿胀测定，利用 Mrgprb2 基因敲除小鼠模型研究鱼腥草注射液引起的 Mrgprb2 相关类过敏反应。此外，通过 RNA 测序分析鱼腥草注射液引起的类过敏反应的转录组谱。
结果
缺乏 Mrgprb2 的小鼠表现出明显减少的肥大细胞脱颗粒、血清组胺释放和后爪肿胀程度。RNA 测序结果表明，Mrgprb2 在 mTOR/AMPK 通路介导的鱼腥草注射液引起的类过敏反应中起着关键作用。有趣的是，我们的结果表明，Mrgprb2 可能参与 Reelin/E-cadherin 轴介导的化合物 48/80 引起的类过敏反应，这表明 Mrgprb2 在鱼腥草注射液和 C48/80 引起的类过敏反应中发挥不同的作用。
结论
本研究报道了 Mrgprb2 在鱼腥草注射液引起的类过敏反应中的作用及其潜在机制。
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