甘草附子汤“辛甘化阳”配伍调控MAPK/Drp1通路改善线粒体功能障碍防治CIPN的机制研究

化疗所致周围神经病变（CIPN）是化疗引起的主要不良反应之一，降低了患者生命质量和存活率，但尚无明确的防治手段。CIPN属中医“痹证”范畴，甘草附子汤是仲景“辛甘化阳”配伍防治“痹证”的代表方剂之一，主治“骨节疼烦，掣痛”等与CIPN之“神经痛”有诸多相似之处。研究发现线粒体功能障碍与CIPN密切相关。前期实验研究显示甘草附子汤可显著改善长春新碱诱导的CIPN，且网络药理学结果提示其防治CIPN的机制与MAPK信号通路密切相关。基于此，提出“甘草附子汤可能通过调控MAPK/Drp1通路改善线粒体功能障碍而防治CIPN”的假说。本项目拟采用在体-离体实验复制CIPN模型，通过现代生物学技术观察甘草附子汤对MAPK/Drp1通路介导线粒体功能障碍相关指标的影响，明确其防治CIPN的机制，为阻断、逆转CIPN进程及发挥其“减毒增效”之功、协同化疗药物抗肿瘤提供实验依据。

As one of the major adverse reactions caused by chemotherapy, chemotherapy inducing peripheral neuropathy(CIPN) greatly reduces the life quality and survival rate of patients, but no clear prevention and treatment methods have been found. CIPN belongs to the category of “bì syndrome” of traditional Chinese medical, Gancao Fuzi Decoction is the representative prescription of medicinal combination of Zhongjing “forming yang with the pungent and sweet” in preventing and treating “bì syndrome”. The prescription mainly “treats symptoms of joint pain, pulling pain”, which shares many similarities with the “neuralgia and abnormal feeling” of CIPN. Modern researches have found that mitochondrial dysfunction is closely related to CIPN. Previous studies have shown that Gancao Fuzi Decoction can significantly improve CIPN induced by vincristine, and the network pharmacological results suggest that the mechanism that Gancao Fuzi Decoction prevent and treat CIPN may be closely associated with MAPK pathway. Based on this, a hypothesis was proposed “Gancao Fuzi Decoction can prevent CIPN through regulating MAPK signal pathway to improving mitochondrial dysfunction”. This project replicates CIPN model through in vitro and in vivo experiments, by observing the change of related indicators in MAPK/DRP1 pathway mediates mitochondrial dysfunction are effected by Gancao Fuzi Decoction, exerting its function of “reducing toxicity and increasing efficiency”, as well as working together with chemotherapeutic drugs against tumors.