华蟾素注射液在临床上广泛用于多种中晚期肿瘤，但在临床使用中存在多种不良反应，其中血管刺激性反应较为严重，对其临床使用产生一定的制约。血管通透性增高或血管渗出是药物引起血管刺激反应的主要病理机制。前期研究中，对华蟾素注射液主要血管刺激物质进行了筛选，结果表明华蟾素注射液，5-羟色胺、蟾蜍特尼定、蟾蜍色胺三种色胺类成分都能导致显著可的血管通透性增高。本项目拟在前期工作基础上，进一步采用兔血管刺激性反应模型、小鼠血管通透性增高模型和体外血管内皮细胞transwell chamber培养模型相结合，通过正向激活、反向抑制两个方向共同阐明Rho/ROCK信号通路在华蟾素注射液诱导的血管刺激性反应中的作用及分子机制，为其血管刺激性作用的防治提供基础依据。

Cinobufacini injection is widely used for a variety of advanced tumors in clinic, but various adverse reactions especially vascular irritation reactions are induced in the process of drug use, which could produce crtain constraints on its clinical use. Vascular hyperpermeability or vascular leakage is the main pathological mechanism of drug-induced vascular irritation reactions. In preliminary studies, the major vascular stimulating substances of Cinobufacini injection screening results showed that Cinobufacini injection and three tryptamine ingredients serotonin, bufotenidine, bufotenine could lead to significant vascular hyperpermeability. This project will use rabbits vascular irritation reaction models and mice vascular hyperpermeability models in vivo and vascular endothelial cell transwell chamber culture models in vitro to illuminate the molecular mechanisms that Rho/ROCK signaling pathway influenced the Cinobufacini injection-induced vascular irritation reactions through two directions of forward activating and reverse inhibition. The project could provide the basis for prediction and prevention of Cinobufacini injection-induced Vascular irritation reactions.