含笑内酯衍生物ACT001对肺纤维化的治疗作用研究

The therapeutic effect of michelolide derivatives ACT001 on pulmonary fibrosis

目的评价含笑内酯衍生物ACT001对肺纤维化(pulmonary fibrosis,PF)的治疗作用及药理机制。方法分别建立由百草枯、博来霉素诱导的两种PF动物模型,在动物一般生活状态、体重、肺系数、肺组织羟脯氨酸及肺组织胶原百分含量、炎症因子、肺组织病理切片等方面评价ACT001的药效,探究ACT001对肺纤维化的治疗作用及初步的药理机制。结果ACT001可改善百草枯和博来霉素诱导的PF小鼠模型的一般生活状态、增加其体重、降低肺泡炎症、降低小鼠肺系数、降低小鼠肺组织羟脯氨酸及胶原百分含量,并且可以调控PF过程中的TGF-β1、TNF-α及IFN-γ等关键细胞因子的表达及上皮-间充质转变(epithelial-mesenchymal transition,EMT)标志蛋白的表达。结论ACT001通过抑制NF-κB的活化,抑制上皮-间充质转变及炎症因子的释放等发挥治疗PF的作用,有望开发为治疗PF的新药。

Aim To evaluate the therapeutic effect of michelolide derivatives ACT001 on the pulmonary fibrosis.Methods Two pulmonary fibrosis(PF)models were established on mice respectively induced by paraquat(PQ)and bleomycin(BLM).When the models built up,ACT001 were administered to PF mice and the treatment effects were evaluated.Results ACT001 obviously improved the general living status of PF mice,increase the body weight of PF mice,reduced the degree of alveolitis and idiopathic pulmonary fibrosis,the lung confficient,the content of hydroxyproline and collagen,and regulated the levels of inflammatory cytokines in serum,such as TGF-β1,TNF-αand IFN-γ.Conclusions ACT001 can alleviate PF by inhibiting the process of epithelial-mesenchymal transition(EMT),inhibiting the activation of NF-κB and decrease the content of inflammatory factors.ACT001 maybe an innovative drug for PF treatment.