Context: Shuxuening injection (SXNI), derived from the leaf of Ginkgo biloba L. (Ginkgoaceae), is widely used to treat cardio-cerebral vascular system related disease due to the efficacy of dilating the blood vessels and improving the function of microcirculation. Nevertheless, SXNI induces immediate hypersensitivity reactions in clinics and the molecular mechanisms are unknown.Objective: The present study investigates the molecular mechanism of SXNI mediated hypersensitivity reactions.Materials and methods: Naive male ICR mice (n = 10) were administered (i.v.) with negative control combined with Evans blue (EB) (CTL-EB), SXNI (14 or 70 mg/kg) combined with EB (SXNI/1-EB or SXNI/4-EB), vascular leakage was evaluated, ears and lungs were collected for histopathological analysis. In vitro, TSC1 was knockdown in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with SXNI, and the alterations of endothelial cell permeability were observed. Rapamycin (mTOR inbibitor) was used to investigate SXNI-induced hypersensitivity reactions both in mice and HUVECs.Results: SXNI (70 mg/kg) induced vascular leakage in mice. Slight oedema and microvascular dilation in the ears, and broaden of alveolar septal and monocyte infiltration in the lungs were observed in SXNI (70 mg/kg) treated mice. mTOR inhibitor alleviates SXNI mediated vascular endothelial hyperpermeability both in vitro and in vivo.Discussion and conclusions: SXNI stimulates pseudo-allergic reactions through hyperactivation of mTOR signalling pathway. Our work provides the new molecular mechanism of drug related pseudo-allergic reactions, and a potential drug to prevent and treat SXNI mediated hypersensitivity reactions.

中文翻译：

---

来自银杏叶的舒血宁注射液通过过度激活 mTOR 诱导假性过敏反应

背景：舒血宁注射液（SXNI）来源于银杏科（Ginkgoaceae）的叶子，具有扩张血管、改善微循环功能的功效，被广泛用于治疗心脑血管系统相关疾病。然而，SXNI 在临床中诱发速发型超敏反应，分子机制尚不清楚。目的：本研究调查 SXNI 介导的超敏反应的分子机制。阴性对照联合伊文思蓝（EB）（CTL-EB），SXNI（14或70mg/kg）联合EB（SXNI/1-EB或SXNI/4-EB），评价血管渗漏，耳肺收集用于组织病理学分析。体外，TSC1 在人脐静脉内皮细胞 (HUVEC) 中被敲低。HUVECs与SXNI一起孵育，观察内皮细胞通透性的改变。雷帕霉素 (mTOR inbibitor) 用于研究 SXNI 诱导的小鼠和 HUVEC 的超敏反应。结果：SXNI (70 mg/kg) 诱导小鼠血管渗漏。在 SXNI (70 mg/kg) 治疗的小鼠中观察到耳朵轻微水肿和微血管扩张，肺泡间隔和单核细胞浸润扩大。mTOR 抑制剂在体外和体内减轻 SXNI 介导的血管内皮高渗透性。讨论和结论：SXNI 通过 mTOR 信号通路的过度激活刺激假过敏反应。我们的工作提供了与药物相关的假性过敏反应的新分子机制，