西南医科大学学报2026，Vol.49Issue(5)：616-622,7.DOI:10.3969/j.issn.2096-3351.2026.05.008
4-辛基衣康酸对压力超负荷所致心力衰竭的作用及机制
Effect and Mechanism of 4-Octyl Itaconate on Pressure Overload-Induced Heart Failure
摘要
Abstract
Objective To investigate the effects of 4-octyl itaconate(4-OI)on pressure-induced heart failure and its potential mechanisms.Methods Thirty 8-week-old male SPF C57BL/6J mice were randomly divided into a sham surgery group(Sham group,n=6),a 4-octyl itaconate group(Sham+4-OI group,n=8),the model group(TAC group,n=8),and the model+4-octyl itaconate group(TAC+4-OI group,n=8).The TAC and TAC+4-OI groups were subjected to transverse aortic constriction(TAC)to establish a model of pressure overload-mediated heart failure.The Sham+4-OI group and the TAC+4-OI group received intraperitoneal injections of a 50 mg/kg 4-OI solution twice a week post-surgery,while the Sham group and the TAC group received intraperitoneal injections of an equal volume,identically formulated blank solvent(without 4-OI)at the same time,for 8 weeks.Cardiac function was assessed by echocardiography,and cardiac parameters were measured(n=6).Hematoxylin-eosin(HE)staining was used to observe cardiac mor-phological changes and inflammatory infiltration in mice from each group,while Sirius red staining was used to assess cardiac collagen deposition.Western blot(n=3)and real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR,n=6)were used to detect the levels of the myocardial fibrosis markers COL3A1 and SERPINE1 in mouse myocardial tissue,and RNA sequencing(RNA-seq,n=6)was employed to explore the potential mechanisms by which 4-OI ameliorates heart failure induced by pressure over-load.Statistical analysis was performed using one-way analysis of variance(ANOVA)and Tukey's test.Results Compared with the Sham group,mice in the TAC group exhibited worsened ventricular remodeling(LVIDd,IVSd,LVPWd)and reduced cardiac func-tion(LVEF,LVFS)(all P<0.05),as well as elevated protein(P<0.05)and mRNA(P<0.001)levels of the myocardial fibrosis mark-ers COL3A1 and SERPINE1.In contrast to the TAC group,mice in the TAC+4-OI group exhibited reduced ventricular remodeling(LVIDd,IVSd,LVPWd)and improved cardiac function(LVEF,LVFS)(all P<0.05),along with decreased protein(P<0.05)and mRNA(P<0.001)expression levels of the myocardial fibrosis markers COL3A1 and SERPINE1.These results suggest that 4-OI exerts a beneficial effect on pressure overload-induced heart failure.By performing RNA-seq on myocardial tissue from mice in each group to identify differentially expressed genes and conducting PPI,GO,and KEGG enrichment analyses,we found that 4-OI intervention regulated the expression of genes such as MMP9,VWF,LCN2,CD163,and LTF.Functional and pathway enrichment analyses of the dif-ferentially expressed genes revealed a strong association with immune-related processes.Conclusion 4-OI improves pressure overload-induced heart failure,and its mechanism may be related to the regulation of the expression of core immune-related genes.关键词
4-辛基衣康酸/心力衰竭/主动脉缩窄/压力超负荷/免疫调节Key words
4-octyl itaconate/Heart failure/Transverse aortic constriction/Pressure overload/Immunoregulation分类
医药卫生引用本文复制引用
李特,刘婷婷,庞金伟,范忠才,杨萍..4-辛基衣康酸对压力超负荷所致心力衰竭的作用及机制[J].西南医科大学学报,2026,49(5):616-622,7.基金项目
四川省科技厅重大科技专项(2025YFRG0005) （2025YFRG0005）
