阿密茴素拮抗多柔比星诱发的组织毒性及其机制研究

多柔比星(Doxorubicin, DOX)是临床上使用最广泛的蒽环家族化疗药物.为了研究阿密茴素(Visnagin, VIS)能否缓解DOX诱发的肝、肾毒性及其相关机制，此研究首先构建DOX急性、慢性肝肾损伤小鼠模型，通过观察小鼠肝肾细胞死亡率、肝肾功能变化评价VIS对肝肾损伤的保护作用.在急性和慢性损伤模型中，原位末端凋亡实验(TUNEL)结果表明VIS可以显著降低肝肾细胞凋亡率；而慢性模型中，VIS还能缓解肝肾功能损伤.此外，实验结果表明VIS可以显著抑制DOX诱发的TOP2-DNA共价复合物形成，提示VIS可能通过抑制DOX下游的TOP2通路起保护作用.研究结果将为后续深入探究降低DOX毒副作用的课题提供参考.

Visnagin antagonizes the tissue toxicity of Doxorubicin and its mechanism

Doxorubicin (DOX) is the most widely used anthracycline family chemotherapeutic drug in clinical practice. In order to study whether Visnagin (VIS) could alleviate DOX-induced hepatotoxicity and nephrotoxicity and its related mechaninsms, this study first constructed a DOX-induced mouse model with acute or chronic liver and kidney injury. Then the protective effect of VIS on liver and kidney injury was evaluated by observing the mortality of mouse liver and kidney cells and the changes of liver and kidney function. The TUNEL results showed that VIS can significantly reduced apoptosis of liver and cells in acute and chronic injury models, and VIS can also relieve liver and kindey damage in the chronic model, in which VIS reduced DOX-induced creatine / urea and ALT/AST levels. In addition, VIS significantly inhibit the formation of the TOP2-DNA covalent complex level induced by DOX, suggesting that VIS may have a protective effect by inhibiting the TOP2 pathway downstream of DOX. The results will shed light on the follow-up in-depth exploration of reducing the side effects of DOX.