中国药理学通报2025，Vol.41Issue(8)：1453-1462,10.DOI:10.12360/CPB202411047
水飞蓟宾衍生物Sil-1调控MAPK信号通路抑制大鼠急性心肌梗死损伤的机制
Mechanism of silibinin derivative Sil-1 modulating MAPK signaling pathway to inhibit acute myocardial infarction in rats
摘要
Abstract
Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.关键词
水飞蓟宾/急性心肌缺血/炎症/氧化应激/蛋白质组学/MAPK信号通路Key words
silibinin/acute myocardial ischemia/in-flammation/oxidative stress/proteomics/MAPK sig-naling pathway分类
医药卫生引用本文复制引用
刘译璠,李梦,崔德宇,卢小艳,宁停波,徐春秀,姚景春,周继栋,刘忠..水飞蓟宾衍生物Sil-1调控MAPK信号通路抑制大鼠急性心肌梗死损伤的机制[J].中国药理学通报,2025,41(8):1453-1462,10.基金项目
国家重点研发计划"中医药现代化专项"(No 2022 YFC3502100) （No 2022 YFC3502100）
