湖南中医药大学学报2025，Vol.45Issue(1)：6-14,9.DOI:10.3969/j.issn.1674-070X.2025.01.002
基于NPNT/JAK2/STAT3信号通路探讨血府逐瘀汤促冠心病血瘀证模型大鼠心肌修复的作用机制
Mechanism of action of Xuefu Zhuyu Decoction in promoting myocardial repair in a rat model of coronary heart disease with blood stasis pattern based on the NPNT/JAK2/STAT3 signaling pathway
摘要
Abstract
Objective To explore the mechanism of action of Xuefu Zhuyu Decoction(XFZYD)in promoting myocardial repair in a rat model of coronary heart disease with blood stasis pattern based on the NPNT/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods A rat model of coronary heart disease with blood stasis pattern was established by ligating the left anterior descending branch of the coronary artery.After successful modeling,the rats were randomized into model group(intragastric administration of an equal volume of distilled water),trimetazidine group[intragastric administration of 5.4 mg/(kg·d)trimetazidine solution],and low-,medium-,and high-dose XFZYD groups(intragastric administration of 3.51,7.02,and 14.04 g/(kg·d)of XFZYD solution,respectively).Additionally,a normal group(no intervention measures)and a sham-operated group(the left anterior descending coronary artery was only threaded but not ligated)were established,and both groups were administered an equal volume of distilled water by gavage.Five rats were in each group,and all were euthanized for tissue collection after seven days of continuous gavage administration.Echocardiography was performed to measure the rat cardiac function indicators;Hemorheological tests were conducted to determine the whole blood viscosity,Casson viscosity,and red blood cell aggregation index;HE staining was used to observe the morphological changes in myocardial tissue;ELISA was employed to measure the expressions of serum platelet-derived growth factor-BB(PDGF-BB),insulin-like growth factor-1(IGF-1),myocardial tissue vascular endothelial growth factor(VEGF),and vascular endothelial cell growth factor receptor-1(VEGFR-1);Western blot was used to examine the protein expressions of JAK2,p-JAK2,STAT3,and p-STAT3 in myocardial tissue;real-time fluorescence quantitative PCR was performed to check the mRNA expressions of NPNT,JAK2,and STAT3 in myocardial tissue.Results Compared with the sham-operated group,the model group showed significant ST-segment elevation on electrocardiogram,lower left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(P＜0.01),higher left ventricular end-diastolic diameter(LVIDd)and left ventricular end-systolic diameter(LVIDs)(P＜0.01),elevated whole blood viscosity(low,medium,and high shear rates),Casson viscosity,and red blood cell aggregation index all(P＜0.01),swollen,fractured,and disordered myocardial cells with numerous inflammatory cells,higher levels of PDGF-BB,IGF-1,VEGF,and VEGFR-1(P＜0.01),elevated protein expressions of p-JAK2 and p-STAT3(P＜0.01),and higher mRNA expression levels of JAK2,STAT3,and NPNT(P＜0.01).Compared with the control group,the treatment groups showed varying degrees of ST-segment reduction on electrocardiogram.The trimetazidine group,medium-dose XFZYD group,and high-dose XFZYD group showed higher LVEF and LVFS(P＜0.01),and lower LVIDd and LVIDs(P＜0.01),while the low-dose XFZYD group showed reduced LVIDd(P＜0.05).The trimetazidine group,medium-dose XFZYD group,and high-dose XFZYD group showed lower whole blood viscosity(low,medium,and high shear rates)(P＜0.01,P＜0.05),while the low-dose XFZYD group showed reduced whole blood viscosity(low shear)and Casson viscosity(P＜0.01,P＜0.05).The myocardial cell morphology and structure were improved to varying degrees in all treatment groups.The trimetazidine group,medium-dose XFZYD group,and high-dose XFZYD group showed higher levels of PDGF-BB,IGF-1,VEGF,and VEGFR-1(P＜0.01,P＜0.05),while the low-dose XFZYD group showed higher levels of IGF-1 and VEGF(P＜0.01,P＜0.05).All treatment groups showed elevated protein expressions of p-JAK2 and p-STAT3(P＜0.01,P＜0.05).The trimetazidine group,medium-dose XFZYD group,and high-dose XFZYD group showed higher mRNA expression levels of NPNT,JAK2,and STAT3(P＜0.01).Conclusion XFZYD can significantly reduce myocardial injury in a rat model of coronary heart disease with blood stasis pattern.Its mechanism may be related to the regulation of the NPNT/JAK2/STAT3 signaling pathway and promotion of angiogenesis.关键词
冠心病/血瘀证/血府逐瘀汤/NPNT/JAK2/STAT3信号通路/心肌修复Key words
coronary heart disease/blood stasis pattern/Xuefu Zhuyu Decoction/NPNT/JAK2/STAT3 signaling pathway/myocardial repair分类
医药卫生引用本文复制引用
王明韵,刘祎,杨漾,田朋,李静,匡慧芳,董靓,张秋雁..基于NPNT/JAK2/STAT3信号通路探讨血府逐瘀汤促冠心病血瘀证模型大鼠心肌修复的作用机制[J].湖南中医药大学学报,2025,45(1):6-14,9.基金项目
湖南省自然科学基金项目(2024JJ8167) （2024JJ8167）
湖南中医药大学2022年度学科建设揭榜挂帅项目(22JBZ005) （22JBZ005）
2023年湖南省研究生科研创新项目(CX20230796) （CX20230796）
湖南中医药大学2023年"一方"研究生创新项目(2023YF07). （2023YF07）
