【摘要】 目的 探讨E3泛素蛋白连接酶TRIM7对鼠源性骨髓巨噬细胞（BMDMs）来源泡沫细胞脂质积累的影响及机制。方法 Western blot和qRT-PCR检测氧化型低密度脂蛋白刺激BMDMs后TRIM7的表达变化；构建TRIM7敲除的BMDMs和TRIM7过表达的THP-1细胞系，通过qRT-PCR、油红O染色和总胆固醇含量检测分析TRIM7对BMDMs脂质代谢的影响；Western blot检测TRIM7敲除后BMDMs中MAPK信号通路蛋白的磷酸化水平；免疫共沉淀检测TRIM7与MAPK通路上游激酶TAK1的相互作用。结果 TRIM7与TAK1存在直接相互作用，TRIM7敲除可通过增强MAPK信号通路蛋白的磷酸化活性，上调CD36和MSR1表达并抑制ABCA1表达，增加胆固醇摄取并减少脂质排出，最终促进泡沫细胞形成。结论 TRIM7通过直接结合TAK1抑制MAPK信号通路及清道夫受体表达，负向调控泡沫细胞脂质积累，为动脉粥样硬化的治疗提供了潜在的新靶点方向。更多还原

【Abstract】 Objective To investigate the effect of TRIM7,an E3 ubiquitin protein ligase,on lipid accumulation in foam cells derived from mouse bone marrow-derived macrophages(BMDMs)and its mechanism.Methods Western blot and qRT-PCR were used to detect the expression changes of TRIM7 in BMDMs stimulated by oxidized low-density lipoprotein.Construct TRIM7 knockout BMDMs and TRIM7 overexpression THP-1 cell lines,and analyze the effect of TRIM7 on lipid metabolism of BMDMs through qRT-PCR,oil red staining,and total cholesterol content detection.Western blot was used to detect the phosphorylation levels of MAPK signaling pathway proteins in BMDMs after TRIM7 knockout.Immunoprecipitation detection of the interaction between TRIM7and the upstream kinase TAK1 in the MAPK pathway.Results TRIM7 interacted directly with TAK1,TRIM7 knockout could enhance the phosphorylation activity of MAPK signaling pathway protein,up regulate the expression of CD36 and MSR1 and inhibit the expression of ABCA1,increase cholesterol uptake and reduce lipid excretion,and ultimately promote the formation of foam cells.Conclusion TRIM7 negatively regulates lipid accumulation in foam cells by inhibiting MAPK signaling pathway and scavenger receptor expression by directly binding to TAK1,which provides a potential new target for the treatment of atherosclerosis.更多还原