海南医科大学学报2025,Vol.31Issue(18):1399-1407,9.DOI:10.13210/j.cnki.jhmu.20241121.003
川陈皮素通过激活Nrf2/HO-1信号通路减轻脓毒症小鼠的心肌损伤
Nobiletin alleviates myocardial injury in septic mice by activating nrf2/ho-1 signaling pathway
摘要
Abstract
Objective:To investigate the effect of nobiletin(NOB)on myocardial injury in septic mice.Methods:Fifty Kun-ming mice were randomly divided into the sham operation(Sham)group,model(CLP)group,model+nobiletin low concen-tration(CLP+NOB-L)group,model+nobiletin high concentration(CLP+NOB-H)group and nobiletin(NOB)single drug group,with 10 mice in each group.Sepsis model was established by cecal ligation and puncture(CLP).The operation of the Sham group and NOB single drug group was the same as that of the CLP group except for cecal ligation and puncture.All mice underwent echocardiography after anesthesia 24 hours after surgery,and then blood and heart samples were collected.The levels of serum TNF-α,IL-1β,CK-MB and cTnⅠ were detected by ELISA.The levels of SOD and MDA in myocardial tissue were detected by oxidative stress kit.HE staining was used to evaluate myocardial pathological changes,the expression level of ROS in myocardial tissue was detected by DHE fluorescent probe.The relative expression of Nrf2/HO-1 pathway was detected by immu-nohistochemistry and Western blot.Results:Compared to the Sham group,LVEF and LVFS in the CLP group were significantly decreased(P<0.05).HE staining of myocardial tissue showed increased inflammatory cell infiltration,serum TNF-α,IL-1β,CK-MB and cTnⅠ levels were significantly increased(P<0.05),myocardial tissue MDA level was increased,SOD activity was decreased(P<0.05),ROS was significantly increased,Nrf2 and HO-1 expression was increased(P<0.05).Compared to the CLP group,the LVEF and LVFS of the CLP+NOB-L group and the CLP+NOB-H group were increased(P<0.05).HE staining of myocardial tissue showed that the infiltration of inflammatory cells was reduced,the contents of serum TNF-α,IL-1β,CK-MB and cTnⅠ were significantly decreased(P<0.05),the level of MDA in myocardial tissue was decreased,the activity of SOD was increased(P<0.05),and ROS was significantly decreased.In addition,compared to the CLP group,the expression of Nrf2 and HO-1 in the CLP+NOB-H group was further increased(P<0.05).Conclusion:Nobiletin may alleviate myocardial in-jury in septic mice by activating Nrf2/HO-1 signaling pathway to inhibit inflammation and oxidative stress.关键词
脓毒症/心肌损伤/川陈皮素/氧化应激/炎症反应/Nrf2/HO-1信号通路Key words
Sepsis/Myocardial injury/Nobiletin/Oxidative stress/Inflammatory reaction/Nrf2/HO-1 signaling pathway分类
医药卫生引用本文复制引用
古雍翔,田勇,周颖,杨国辉..川陈皮素通过激活Nrf2/HO-1信号通路减轻脓毒症小鼠的心肌损伤[J].海南医科大学学报,2025,31(18):1399-1407,9.基金项目
This study was supported by Guizhou Medical University National Natural Science Foundation Cultivation Project(gyfynsfc-2021-54) 贵州医科大学国家自然科学基金培育项目(gyfynsfc-2021-54) (gyfynsfc-2021-54)