目的 揭示蟾酥提取物对大鼠胸主动脉血管环舒缩的双向调控作用及潜在效应成分组成。方法 利用离体生物能量信号采集系统，评价蟾酥提取物及其水洗脱部位和70%乙醇洗脱部位对大鼠胸主动脉血管环的舒缩调控作用；并在此基础上，建立UHPLC-Q TOF-MS/MS联用方法，对各样品进行成分解析；根据成分鉴定结果，逐一考察其中主要成分的血管调控效应。结果 蟾酥提取物对静息状态下的大鼠胸主动脉血管环表现出先收缩后舒张的双向调控作用；而其水洗脱部位仅表现出血管收缩效应，70%乙醇洗脱部位仅表现出血管舒张效应。进一步研究发现，肾上腺素、5-羟色胺是蟾酥提取物水洗脱部位中发挥血管收缩效应的主要成分；而华蟾酥毒基、酯蟾毒配基、华蟾毒它灵、去乙酰华蟾毒精和脂蟾毒精是蟾酥提取物70%乙醇洗脱部位中发挥血管舒张效应的主要成分。结论 蟾酥提取物对于血管舒缩的双向调控作用，与其中水溶性成分肾上腺素、5-羟色胺诱导血管收缩，脂溶性成分华蟾酥毒基、酯蟾毒配基、华蟾毒它灵、去乙酰华蟾毒精和脂蟾毒精诱导血管舒张密切相关，为中药单味药多成分作用于同一器官的多靶点协同拮抗调控效应研究提供了数据支撑。

Objective To reveal the bidirectional regulation of Chansu (Bufonis Venenum) extract on the relaxation and contraction of thoracic aorta rings in rats, and to clarify its potential effective components. Methods Firstly, the in vitro bioenergy signal acquisition system was employed to evaluate the effects of Bufonis Venenum extract and its water elution fraction and 70% ethanol elution fraction on the vasomotor regulation of thoracic aorta vascular rings in rats. Subsequently, the UHPLC-Q TOF-MS/MS method was established to analyze the components of those above samples. After that, in accordance with the components identification results, the vascular regulation effects of the main components identified above were detected one by one. Results The extract of Bufonis Venenum showed bidirectional regulation effects on the thoracic aorta vascular rings in rats. While, its water elution fraction only showed vasoconstriction effects, and its 70% ethanol elution fraction only exhibited vasodilation effects. Further investigation demonstrated that L-adrenaline and 5-hydroxytryptamine were the main effective components of vasoconstriction contained in water elution fraction, and cinobufagin, resibufogenin, cinobufotalin, desacetylcinobufagin and resibufagin were the main effective components of vasodilation contained in 70% ethanol elution fraction. Conclusion The bidirectional regulation effects of Bufonis Venenum extract on thoracic aorta vascular rings in rats were result from the simultaneous regulation of the water-soluble components to induce vasoconstriction and the fat-soluble components to induce vasodilation. This study provides data supports for the investigation of synergistic antagonistic regulatory effects of multiple components contained in one traditional Chinese medicine acting on multiple targets on one same organ.

R285;R284

国家自然科学基金重点项目（81930113）；国家自然科学基金面上项目（81774155）；博士后科学基金面上项目（2020M680472）