实用医学杂志2024，Vol.40Issue(17)：2381-2389,9.DOI:10.3969/j.issn.1006-5725.2024.17.005
ALKBH5通过TRAF1/NF-κB通路减轻脓毒症心肌损伤的机制
ALKBH5 reduce septic-induced myocardial dysfunction by regulating the TRAF1/NF-κB pathway
摘要
Abstract
Objective To investigate the molecular mechanism of ALKBH5 reducing sepsis-induced myocardial dysfunction(SIMD).Methods The expression levels of ALKBH5 and TRAF1 in the blood of 50 SIMD patients and 50 healthy individuals were detected using reverse transcription fluorescence quantitative polymerase chain reaction(RT-qPCR),and the correlation between their expression levels was analyzed by person analysis;In vitro experiments,H9C2 myocardial cells were divided into 7 groups according to over expression of TARF1 and knockdown ALKBH5.The molecular mechanism of ALKBH5 targeting TRAF1 to regulate lipopolysaccharide(LPS)induced myocardial cell damage was studied through experiments such as CCK8,ELISA,and Western blot;In the in vivo experiment of rats,LPS induced rats were divided into 6 groups according to over expression of TARF1 and knockdown ALKBH5.Experimental methods such as colorimetry,ELISA,Western blot,HE staining,and immuno-histochemistry were used to study the mechanism of ALKBH5 targeting TRAF1 through NF-κB pathway in reduc-ing myocardial cell damage.Results The expression levels of ALKBH5 and TRAF 1 were downregulated in SIMD,and the Pearson analysis showed a positive correlation between them(P<0.001);In vitro experiments showed that overexpression of TRAF1 promotes cell proliferation,inhibits the expression of inflammatory factors and proteins involved in the NF-κB pathway,and knockdown ALKBH5 obtain the opposite resulst;In vivo experi-ments in rats showed that knockdown ALKBH5 promotes injury in cardiomyocytes,expression of inflammatory factors and NF-κB-related pathway proteins,and nuclear translocation of NF-κB p65 protein,but the overexpression of TRAF 1 yielded the opposite results.Conclusion ALKBH5 increases the stability of TRAF1 by reducing its meth-ylation,thereby inhibiting NF-κB pathway,thereby reducing SIMD.关键词
脓毒症心肌损伤/ALKBH5/TRAF1/NF-κBKey words
sepsis-induced myocardial dysfunction/ALKBH5/TRAF1/NF-κB分类
医药卫生引用本文复制引用
刘敏,陈喜云,吕建磊,冯洁..ALKBH5通过TRAF1/NF-κB通路减轻脓毒症心肌损伤的机制[J].实用医学杂志,2024,40(17):2381-2389,9.基金项目
湖南省自然科学基金项目(编号:2024JJ9508) （编号:2024JJ9508）
湖南省卫生健康委科研计划项目(编号:B202317017605) （编号:B202317017605）
