State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China.
Department of Immunology, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China.
Pharmacol Res. 2017 Nov;125(Pt B):150-160. doi: 10.1016/j.phrs.2017.08.014. Epub 2017 Sep 1.
Zhengqing Fengtongning (ZQFTN), the pharmaceutical preparation of sinomenine (SIN) derived from the medicinal plant Sinmenium acutum, is well-known in China as an effective treatment for rheumatoid arthritis (RA). However, its histamine-release anaphylactoid reactions (HRARs) occur often in some patients. Therefore, it is desirable to establish effective clinical protocols to manage such HRARs. In the study, rat models with systemic HRARs and local HRARs of the skin were established. The level of vascular permeability and mast cell numbers was determined by quantitative analysis using Evans blue dye and histological assays. The levels of histamine, leukotriene B4 (LTB4) and IL-33 in plasma were detected by UHPLC-SPE-MS, ELISA and immunohistochemistry assays, respectively. The results demonstrated that SIN significantly induced both systemic and local HRARs in rats, showing significant decrease of body temperature, increases in vascular permeability in skin, injury of lung tissues and mast cell infiltration and IL-33 expression in skin and lung tissues. Mechanistic study showed that tranilast could prevent SIN-triggered HRARs via inhibition of H1 receptor gene expression and NF-κB signaling. Our findings provide evidence that mast cell membrane stabilizers and H1 receptor blockers effectively prevent SIN-induced HRARs, and cromolyn, cetirizine and tranilast can be used in the clinic for the management of HRARs induced by ZQFTN.
正清风痛宁（ZQFTN）是从青风藤植物中提取的盐酸青藤碱的药物制剂，在中国被广泛用于治疗类风湿关节炎（RA）。然而，它会引起一些患者的组胺释放型过敏反应（HRARs）。因此，建立有效的临床方案来管理此类 HRARs 是非常有必要的。在本研究中，建立了全身性和皮肤局部 HRAR 大鼠模型。通过伊文思蓝染料定量分析和组织学检测，确定血管通透性和肥大细胞数量。通过 UHPLC-SPE-MS、ELISA 和免疫组化检测法，检测血浆中组胺、白三烯 B4（LTB4）和 IL-33 的水平。结果表明，SIN 可显著诱导大鼠的全身性和局部 HRARs，表现为体温明显下降，皮肤血管通透性增加，肺组织损伤，肥大细胞浸润和皮肤及肺组织中 IL-33 的表达增加。机制研究表明，曲尼司特可通过抑制 H1 受体基因表达和 NF-κB 信号通路来预防 SIN 触发的 HRARs。本研究结果表明，肥大细胞膜稳定剂和 H1 受体阻滞剂可有效预防 SIN 诱导的 HRARs，曲尼司特、西替利嗪和色甘酸钠可用于临床治疗 ZQFTN 引起的 HRARs。
