时珍国医国药2025，Vol.36Issue(15)：2827-2832,6.DOI:10.70976/j.1008-0805.SZGYGY-2025-1505
参附注射液调控TIMP-3/MMP-1/syndecan-1通路改善脓毒症大鼠心肌损伤的机制研究
Study on the Mechanism of Shenfu Injection Regulating TIMP-3/MMP-1/syndecan-1 Pathway to Improve Myocardial Injury in Rats with Sepsis
摘要
Abstract
Objective To investigate the mechanism by which Shenfu Injection(参附注射液,SFI)alleviates myocardial injury in septic Sprague-Dawley(SD)rats through regulating the TIMP-3/MMP-1/syndecan-1 pathway.Methods A septic model of rats was es-tablished using cecal ligation and puncture(CLP).Forty rats were randomly divided into the sham,CLP,SFI low-dose(SFL)and high-dose(SFH)groups.Serum levels of brain natriuretic peptide(BNP)and troponin I(TnI)were measured,myocardial ultrastruc-ture was observed via electron microscopy(EM),and protein expressions of TIMP-3,MMP-1,and syndecan-1 were quantified u-sing Western blot(WB).Additionally,TIMP-3 knockout(KO)septic model rats were generated to validate the pathway,while serum and myocardial MMP-1/syndecan-1 levels were analyzed across groups.Results The SFI-treated groups exhibited significantly ele-vated serum BNP and TnI levels compared to the CLP group(P＜0.05,P＜0.01),demonstrating dose-dependent efficacy.EM re-vealed reduced endothelial swelling and preserved vascular endothelial glycocalyx integrity in the treatment groups.WB analysis showed that SFI administration significantly increased myocardial TIMP-3 and syndecan-1 expressions(P＜0.05,P＜0.01)and reduced MMP-1 levels(P＜0.01)compared to the CLP group,with superior effects observed in the SFH group versus the SFL group(P＜0.05).In TIMP-3-KO models,serum MMP-1/syndecan-1 levels were markedly elevated(P＜0.01),while myocardial TIMP-3 expression was decreased(P＜0.05),MMP-1 increased(P＜0.01),and syndecan-1 decreased(P＜0.05)compared to the CLP group.The TIMP-3-KO+SF group showed no significant differences compared to TIMP-3-KO(P＞0.05)but displayed sig-nificantly lower TIMP-3/syndecan-1(P＜0.01)and higher MMP-1(P＜0.01)compared to the SFI group.Conclusion SFI in-creased the expression of TIMP-3 and decreased the expression of MMP-1,thereby reducing the degradation of syndecan-1 and alle-viating myocardial injury in septic rats.关键词
参附注射液/脓毒症心肌损伤/TIMP-1/syndecan-1/MMP-1/糖萼Key words
Shenfu Injection(参附注射液)/Sepsis-induced myocardial injury/TIMP-1/Syndecan-1/MMP-1/Glycocalyx分类
医药卫生引用本文复制引用
孙海燕,刘杨,刘茜,孟宪卿,郝浩..参附注射液调控TIMP-3/MMP-1/syndecan-1通路改善脓毒症大鼠心肌损伤的机制研究[J].时珍国医国药,2025,36(15):2827-2832,6.基金项目
国家自然科学基金(82374234 （）
82374242) （）
山东省医药卫生科技发展计划项目(202110000693) （202110000693）
