陕西医学杂志2024，Vol.53Issue(7)：873-878,883,7.DOI:10.3969/j.issn.1000-7377.2024.07.002
毛蕊异黄酮靶向高迁移率族蛋白1对心肌缺血再灌注损伤大鼠保护作用实验研究
Protective effect of calycosin targeting high mobility group box 1 on myocardial ischemia-reperfusion injury in rats
摘要
Abstract
Objective:To probe the phylactic impact and mechanism of calycosin on myocardial ischemia-reper-fusion injury(MIRI)in rats.Methods:A rat model of myocardial ischemia-reperfusion injury was established in SPF SD rats.They were randomly divided into four groups:sham group,MIRI group,low-dose calycosin group and high-dose calycosin group.H9C2 cells were divided into four groups:control group,hypoxia/reoxygenation group,calyco-sin group and HMGB1 protein group.Cardiac function was evaluated by echocardiography.ELISA was used to meas-ure myocardial marker enzymes.HE staining was used to observe the pathological changes of myocardial tissue.TUNEL staining was used to detect the apoptosis of myocardial tissue and H9C2 cells.PPI network was used to ana-lyze the target prediction and molecular docking of calycosin.Cell viability was detected by CCK8 assay.The expres-sion of HMGB1 in myocardium was detected by immunofluorescence.Western blot was used to detect the relative ex-pression levels of HMGB1,Toll-like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65)and Cleaved caspase-3.Results:Compared with the sham group,LVEDD and LVESD were up-regulated,while LVEF and LVFS were down-regulated in MIRI group(all P＜0.05).Myocardial fibers were disrupted and inflammatory cell infiltration in-creased.Serum CK-MB,LDH and cTnI levels were significantly increased,the number of TUNEL positive cells and the level of Cleaved caspase-3 were increased,and the expression of HMGB1 was increased(all P＜0.05).Compared with the MIRI group,LVEDD and LVESD in the low-and high-dose calycosin groups were down-regulated(all P＜0.05),while LVEF and LVFS were up-regulated(all P＜0.05),and the arrangement of myocardial fibers was still regular,and the number of inflammatory cells was small,and the serum levels of CK-MB,LDH and cTnI decreased,and the number of TUNEL positive cells and the level of Cleaved caspase-3 were decreased,and the expression of HMGB1 was decreased(all P＜0.05).PPI and molecular docking showed that calycosin could bind to HMGB1.Compared with the control group,the number of TUNEL positive H9C2 cells in the hypoxia/reoxygenation group was significantly increased,and the expression of Cleaved caspase-3,HMGB1,TLR4 and NF-κB p65 was up-regulated(all P＜0.05).Compared with the hypoxia/reoxygenation group,the number of TUNEL positive cells and the ex-pression of Cleaved caspase-3,HMGB1,TLR4 and NF-κB p65 were decreased in the calycosin group(all P＜0.05).However,the protective effect of calycosin was reversed when calycosin was added to rHMGB1 in the calycosin group.Conclusion:Calycosin can significantly improve MIRI in rats possibly by inhibiting the HMGB1/TLR4/NF-KB pathway.关键词
心肌缺血再灌注损伤/毛蕊异黄酮/高迁移率族蛋白1/炎症/细胞凋亡/Toll样受体4/核因子-κB通路Key words
Myocardial ischemia-reperfusion injury/Calycosin/High mobility group box-1 protein/Inflamma-tion/Apoptosis/TLR4/NF-κB pathway分类
医药卫生引用本文复制引用
赵明慧,薛凌..毛蕊异黄酮靶向高迁移率族蛋白1对心肌缺血再灌注损伤大鼠保护作用实验研究[J].陕西医学杂志,2024,53(7):873-878,883,7.基金项目
辽宁省自然科学基金资助项目(20170540372) （20170540372）
锦州医科大学附属第三医院青苗院长基金资助项目(FSSYQM2020004) （FSSYQM2020004）
