硬脂酰辅酶A去饱和酶1通过抑制肺上皮细胞铁死亡缓解小鼠特发性肺纤维化进展的作用研究  

Stearoyl-CoA desaturase 1 mitigates the progression of mouse idiopathic pulmonary fibrosis in mice by inhibiting ferroptosis of pulmonary epithelial cells

作　　者：吴趋荟 李妲[1] 符艳 侯钰丛 张琴[1] 金朝晖[1] WU Qu-hui;LI Da;FU Yan;HOU Yu-cong;ZHANG Qin;JIN Zhao-hui(The First Hospital of Hunan University of Chinese Medicine,Changsha 410208)

机构地区：[1]湖南中医药大学第一附属医院,长沙410208

出　　处：《中南药学》2024年第5期1141-1149,共9页Central South Pharmacy

基　　金：湖南省卫健委重点项目(No.202203023299);长沙市自然科学基金项目(No.kq2202455);湖南省教育厅科学研究项目(No.22A0252)。

摘　　要：目的 拟利用基因敲除小鼠和细胞系研究硬脂酰辅酶 A 去饱和酶 1(SCD1)在特发性肺纤维化(IPF)中的作用及机制。方法 利用SCD1条件敲除小鼠和BEAS-2B细胞,比较SCD1敲除或敲低后组织学改变和铁死亡变化,并研究PPARα激动剂Fenofibrate对SCD1表达和对IPF的影响。结果 敲除SCD1会加重IPF、上调纤维化相关蛋白水平并降低GPX4表达;敲低SCD1会提高脂质氧化水平、促进肺上皮细胞铁死亡,而Fenofibrate可上调SCD1表达,降低细胞铁死亡和IPF严重程度。结论 研究结果证实抑制SCD1会促进肺上皮细胞铁死亡、加重IPF,而Fenofibrate可通过上调SCD1表达治疗IPF。本研究将为防控IPF提供潜在靶点和候选药物。Objective To determine the role and mechanism of stearoyl-CoA desaturase 1(SCD1)in idiopathic pulmonary fibrosis(IPF)with gene knockout mice and cell lines.Methods SCD1 conditional knockout mice and BEAS-2B cells were used to compare the histological changes and ferroptosis alteration after SCD1 knockout or knockdown.The effect of the PPARαagonist Fenofibrate on SCD1 expression and its impact on IPF were also examined.Results The knockout of SCD1 worsened IPF,upregulated the levels of fibrosis-related proteins,and decreased GPX4 expression.The knockdown of SCD1 increased the lipid oxidation levels,promoted ferroptosis of epithelial cells in the lung,while Fenofibrate upregulated SCD1 expression,reduced the cellular ferroptosis,and ameliorated the severity of IPF.Conclusion SCD1 inhibition promotes the ferroptosis of epithelial cells in the lung,exacerbating IPF,while Fenofibrate can be used to treat IPF by upregulating the SCD1 expression.This study provides potential targets and candidate drugs for the prevention and control of IPF.

关 键 词：特发性肺纤维化 铁死亡 硬脂酰辅酶A去饱和酶1 FENOFIBRATE 

分 类 号：R96[医药卫生—药理学]