前期研究中发现肿瘤治疗药物华蟾素注射液及其组分5-羟色胺、蟾毒色胺和蟾蜍特尼定能够不同程度的激活RhoA/ROCK信号通路使细胞骨架结构发生变化，导致内皮细胞血管通透性增加，且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。由于成分的复杂性，中药制剂具有多靶点调节、多途径作用机制的特征。本项目通过ROCK通路下游ERM蛋白，对与ERM相关的其他途径PLC/PKC和p38-MAPK 信号通路开展进一步研究，通过体内外实验模型，阐明华蟾素注射液及其组分致血管刺激性反应的生物学机制，寻找华蟾素注射液中已筛选出的刺激性物质的多作用靶点，并为其他药物的刺激性反应研究提供数据基础。

In previous studies, we have found that the tumor treatment drug Cinobufacini injection and its components serotonin, bufotenine and bufotenidine could activate the RhoA/ROCK signaling pathway in different levels, resulting in changes in cytoskeletal structure, and then leading to vascular hyperpermeability of endothelial cells. Vascular hyperpermeability or vascular leakage is the main pathological mechanism of drug-induced vascular irritation reactions. Due to the complexity of the composition, the traditional Chinese medicine preparation has the characteristics of multi-target regulation and multi-signal pathway mechanisms. This project further studies the PLC/PKC and p38-MAPK signaling pathways related to ERM proteins, which are downstream proteins of the ROCK pathway. It can verify the biological mechanism of vascular irritant responses induced by Cinobufacini injection and its components through the experimental models in vitro and in vivo, find multi-targets of irritant substances in Cinobufacini injection and provide the data basis for prediction and prevention of other drugs induced vascular irritant responses.