Article(id=1322954428218745129, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1322954407050092740, articleNumber=null, orderNo=null, doi=10.16016/j.2097-0927.202508058, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1755532800000, receivedDateStr=2025-08-19, revisedDate=1757865600000, revisedDateStr=2025-09-15, acceptedDate=null, acceptedDateStr=null, onlineDate=1793346514991, onlineDateStr=2026-10-30, pubDate=1760457600000, pubDateStr=2025-10-15, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793346514991, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793346514991, creator=13701087609, updateTime=1793346514991, updator=13701087609, issue=Issue{id=1322954407050092740, tenantId=1146029695717560320, journalId=1319373162502258839, year='2025', volume='47', issue='19', pageStart='2289', pageEnd='2444', issueExtLink='null', onlineDate='null', pubDate='1760457600000', pubDateStr='2025-10-15', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793346509945, creator='13701087609', updateTime=1793346509945, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=2374, endPage=2384, ext={EN=ArticleExt(id=1322954428436848938, articleId=1322954428218745129, tenantId=1146029695717560320, journalId=1319373162502258839, language=EN, title=Muscone improves coronary microvascular disease by promoting VEGF-mediated microvascular angiogenesis, columnId=1320434418116837551, journalTitle=Journal of Army Medical University, columnName=Basic Medicine, runingTitle=null, highlight=null, articleAbstract=
Objective To explore the impact of Shexiang Baoxin Pill (SXBXP, a traditional Chinese patent medicine, broadly applied for the treatment of cardiovascular diseases) on coronary microvascular disease (CMD) and investigate the role and underlying mechanisms of muscone, a key bioactive component of the pills, in the treatment.
Methods A total of 16 ob/ob mice (8 weeks old) were randomly and equally divided into an ob/ob-SXBXP group and a ob/ob-Control group, receiving 10 mg/kg·d SXBXP or PBS via oral gavage, and another 8 wild-type mice with the same genetic background (WT group) were subjected as a negative control group. Cell model of CMD was established based on mouse coronary microvascular endothelial cells (MCMEC) under ischemia and hypoxic (HI) condition, and the cells were further treated with 20 μg/mL SXBXP (HI+SX) and 30 μmol/L muscone (HI+Muscone), respectively. Echocardiography was carried out for coronary flow reserve (CFR) and left ventricular function, and laser speckle imaging was applied to evaluate myocardial blood flow (MBF). Microvascular density in the heart was evaluated with CD31 immunofluorescence staining. The expression levels of vascular endothelial growth factor (VEGF) in cardiac microvascular endothelial cells of both mouse and cell models were detected by immunofluorescence staining and Western blot analysis. The proliferation and angiogenesis of MCMEC were observed by 5-ethynyl-2'-deoxyuridine staining and angiogenesis experiments.
Results In the ob/ob-Control group of mice, the levels of CFR, MBF, and cardiac microvascular density were significantly lower than those in the WT group (P<0.05), and these indicators were significantly improved in the ob/ob-SXBXP group when compared with the ob/ob-Control group (P<0.05), which indicates that SXBXP improves the CMD phenotype. The expression level of VEGF in cardiac microvascular endothelial cells was significantly lower in the ob/ob-Control mice than the WT mice (P<0.05), while the level in the ob/ob-SXBXP group was significantly higher than that in the ob/ob-Control group (P<0.05), illustrating that SXBXP may ameliorate CMD through VEGF-mediated microvascular angiogenesis. In vitro experiments further revealed that the VEGF expression level and the proliferation and angiogenesis abilities in MCMEC were significantly lower in the HI group than the cells under the normoxia control condition (P<0.05). Both SXBXP and muscone treatment resulted in enhanced expression of VEGF and improved proliferative and angiogenesis abilities of MCMEC (P<0.05). These results suggest that muscone could improve CMD by VEGF-mediated microvascular angiogenesis.
Conclusion SXBXP can improve CMD. Muscone, as a key component of SXBXP, promotes microvascular angiogenesis by inducing the expression of VEGF, then enhances myocardial perfusion, and consequently alleviates CMD.
, authors=Ziyang WANG
1, Dingyuan TIAN
1, Pan ZHENG
1, Ming CHEN
1, Zimeng ZHENG
1, Fang DENG
2, Zhihui ZHANG
1, authorsList=Ziyang WANG, Dingyuan TIAN, Pan ZHENG, Ming CHEN, Zimeng ZHENG, Fang DENG, Zhihui ZHANG, authorCompany=null, correspAuthors=Zhihui ZHANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=© 2025 Journal of Army Medical University, copyrightOwner=Editorial Office of Journal of Army Medical University, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322954429955186999, articleId=1322954428218745129, tenantId=1146029695717560320, journalId=1319373162502258839, language=CN, title=麝香酮通过促进VEGF表达介导的微血管生成改善冠状动脉微血管疾病, columnId=1320434418343329969, journalTitle=陆军军医大学学报, columnName=论著·基础医学, runingTitle=null, highlight=null, articleAbstract=
目的 探讨麝香保心丸(shexiang baoxin pill,SXBXP)对冠状动脉微血管疾病(coronary microvascular disease,CMD)的影响以及麝香酮(Muscone)作为SXBXP中的有效成分对CMD的作用及机制。
方法 8周龄的ob/ob小鼠按照每天10 mg/kg SXBXP(SXBXP组)或无菌PBS(Ctl组)进行灌胃,同背景野生型小鼠(WT组)作为阴性对照;以缺血缺氧干预小鼠冠脉微血管内皮细胞(mouse coronary microvascular endothelial cell,MCMEC)构建CMD细胞模型(HI组),并以20 μg/mL浓度的SXBXP(HI+SX)和30 μmol/L浓度的Muscone(HI+Muscone)分别进行药物干预。通过心脏超声动态评估冠状动脉血流储备(coronary flow reserve,CFR)水平和左心室功能,激光散斑成像评估心肌血流量(myocardial blood flow,MBF)水平。通过CD31免疫荧光染色评估小鼠心脏微血管密度。通过免疫荧光染色和Western blot检测心脏微血管内皮细胞的血管内皮生长因子(Vascular endothelial growth factor,VEGF)表达。5-乙炔基-2-脱氧嘧啶核苷染色、血管生成实验检测MCMEC的增殖能力和成管能力。
结果 ob/ob-Control组小鼠CFR、MBF水平和心脏微血管密度均比WT组小鼠显著降低(P<0.01),ob/ob-SXBXP 组小鼠的上述指标均显著高于ob/ob对照组(P<0.05),表明SXBXP对CMD表型具有改善作用。ob/ob-Control组小鼠心脏微血管内皮细胞VEGF表达水平比WT组小鼠显著降低(P<0.05),而ob/ob-SXBXP组小鼠心脏微血管内皮细胞VEGF表达水平显著高于ob/ob-Control组(P<0.05),SXBXP可能通过VEGF介导的微血管生成改善CMD。体外实验进一步显示,缺血缺氧组(HI)组的VEGF表达水平及MCMEC的增殖和成管能力均显著低于常氧培养(Ctl组)(P<0.05),缺血缺氧SXBXP干预组(HI+SX)和缺血缺氧Muscone干预组(HI+Muscone)上述指标均显著高于HI组(P<0.05),Muscone作为SXBXP的活性物质通过VEGF介导的微血管生成改善CMD。
结论 SXBXP对CMD具有改善作用;Muscone 作为SXBXP中的主要成分通过诱导VEGF的表达促进冠状动脉微血管生成,增加心肌灌注水平从而改善CMD。
, authors=汪紫阳
1, 田丁元
1, 郑攀
1, 陈铭
1, 郑紫梦
1, 邓芳
2, 张志辉
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1Department of Cardiovascular Medicine,First Affiliated Hospital, Faculty of High Altitude Military Medicine,Army Medical University (Third Military Medical University),Chongqing,China), AuthorCompanyExt(id=1322954431779709242, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, companyId=1322954431758737720, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=
1陆军军医大学(第三军医大学):第一附属医院心血管内科)]), AuthorCompany(id=1322954431901344059, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, xref=2, ext=[AuthorCompanyExt(id=1322954431913926972, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, companyId=1322954431901344059, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=
2Department of Pathophysiology, Faculty of High Altitude Military Medicine,Army Medical University (Third Military Medical University),Chongqing,China), AuthorCompanyExt(id=1322954431922315581, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, companyId=1322954431901344059, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=
2陆军军医大学(第三军医大学):高原军事医学系病理生理学教研室)])], figs=[ArticleFig(id=1322954436112425325, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, language=EN, label=Figure 1, caption=
Effects of SXBXP on CFR,MBF,and left heart function in mice, figureFileSmall=ydFA7wiwpr9GGBDdItj8Vg==, figureFileBig=EOOsmRzqYacAmXitLQB5FA==, tableContent=null), ArticleFig(id=1322954436200505710, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, language=CN, label=图1, caption=
SXBXP对小鼠CFR、MBF和左心功能的影响A:Ultrasonic assessment of CFR in mice; B:Bar graph depicting CFR in mice; C:Laser speckle imaging for MBF; D:Bar graph showing MBF in mice; n=8. CFR:Coronary flow reserve; MBF:Myocardial blood flow; EF:Ejection fraction; FS:Fractional shortening. a: P<0.05,b:P<0.01,c:P<0.001,d:P<0.0001 compared with the ob/ob-Control group
, figureFileSmall=ydFA7wiwpr9GGBDdItj8Vg==, figureFileBig=EOOsmRzqYacAmXitLQB5FA==, tableContent=null), ArticleFig(id=1322954436368277871, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, language=EN, label=Figure 1(continued), caption=
Effects of SXBXP on CFR,MBF,heart ventricular function in mice, figureFileSmall=1t+SswwQFllunDX1l0nMgw==, figureFileBig=RFqj6p0dVl1IKMTqQ/fqBA==, tableContent=null), ArticleFig(id=1322954436443775344, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, language=CN, label=续图1, caption=
SXBXP对小鼠CFR、MBF和左心功能的影响E:Echocardiogram for cardiac function in mice:F:Bar graph presenting EF and FS of the hearts in mice(n=8). CFR:Coronary flow reserve; MBF:Myocardial blood flow; EF:Ejection fraction; FS:Fractional shortening. a: P<0.05,b:P<0.01,c:P<0.001,d:P<0.0001,compared with the ob/ob-Control group
, figureFileSmall=1t+SswwQFllunDX1l0nMgw==, figureFileBig=RFqj6p0dVl1IKMTqQ/fqBA==, tableContent=null), ArticleFig(id=1322954436531855729, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, language=EN, label=Figure 2, caption=
Correlation of cardiac microvascular density with CFR and MBF in mice, figureFileSmall=upc7WSP1Juu+0/9gizJlgw==, figureFileBig=TEJmpJtWQWfWX+Z1LkAVRQ==, tableContent=null), ArticleFig(id=1322954436603158898, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, language=CN, label=图2, caption=
小鼠的心脏微血管密度及其与CFR、MBF间的相关性评估A:Immunofluorescence staining of microvascular density in the hearts of mice; B:Bar graph depicting the microvascular density in the hearts of mice; C:Correlation analysis of cardiac microvascular density,MBF,and CFR. CFR:Coronary flow reserve; MBF:Myocardial blood flow. a:P<0.05,b:P<0.01,compared with the ob/ob-Control group
, figureFileSmall=upc7WSP1Juu+0/9gizJlgw==, figureFileBig=TEJmpJtWQWfWX+Z1LkAVRQ==, tableContent=null), ArticleFig(id=1322954436712210803, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, language=EN, label=Figure 3, caption=
Effect of SXBXP intervention on the expression level of VEGF in the heart of mice, figureFileSmall=q8F4l+rhuwq3gsFKtndrcg==, figureFileBig=tbEkZTMbBTAoOTn3em6BNA==, tableContent=null), ArticleFig(id=1322954436779319668, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, language=CN, label=图3, caption=
SXBXP干预对小鼠心肌组织中VEGF表达水平的影响A:Double fluorescence staining for CD31 and VEGF in the hearts; B:Quantitative results of double fluorescence staining of CD31 and VEGF in the hearts; C:Correlation analysis between the relative protein levels of CD31 and VEGF in the mice heart; D:Western blotting for VEGF expression in the hearts; E:Relative expression of VEGF protein in the hearts. SXBXP:Shexiang Baoxin Pills; VEGF:Vascular endothelial growth factor. a:P<0.05,b:P<0.01 compared with the ob/ob-Control group
, figureFileSmall=q8F4l+rhuwq3gsFKtndrcg==, figureFileBig=tbEkZTMbBTAoOTn3em6BNA==, tableContent=null), ArticleFig(id=1322954436859011445, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, language=EN, label=Figure 4, caption=
Effects of SXBXP on VEGF expression,proliferation,and angiogenesis of MCMEC, figureFileSmall=wA10soqGQsEfG0wAW8aeFA==, figureFileBig=YAwaHu5I2tyTAF3qNdQjKQ==, tableContent=null), ArticleFig(id=1322954436934508918, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, language=CN, label=图4, caption=
SXBXP对MCMEC的VEGF表达及增殖和成管能力的影响A:Fluorescence double staining for CD31 and VEGF in MCMEC; B:Quantitative analysis of fluorescence double staining for CD31 and VEGF in MCMEC; C:EdU cell proliferation staining in MCMEC; D:Histogram of the proliferation of MCMEC; E:Microscopic images of angiogenesis in MCMEC; F:Histogram of the angiogenesis of MCMEC. MCMEC:Mouse coronary microvascular endothelial cells; SXBXP:Shexiang Baoxin Pills; VEGF:Vascular endothelial growth factor. a:P<0.05,b:P<0.01,compared with the HI group
, figureFileSmall=wA10soqGQsEfG0wAW8aeFA==, figureFileBig=YAwaHu5I2tyTAF3qNdQjKQ==, tableContent=null), ArticleFig(id=1322954437010006391, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, language=EN, label=Figure 5, caption=
Effects of muscone on VEGF expression,proliferation,and angiogenesis of MCMEC, figureFileSmall=8YDDyee7sbhhRUTNmN/4Iw==, figureFileBig=0sUP5s7fLkpmLmO7lySgxA==, tableContent=null), ArticleFig(id=1322954437068726648, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954428218745129, language=CN, label=图5, caption=
Muscone对MCMEC的VEGF表达及增殖和成管能力的影响A:Fluorescence double staining for CD31 and VEGF in MCMEC; B:Quantitative analysis of fluorescence double staining for CD31 and VEGF in MCMEC; C:EdU cell proliferation staining in MCMEC; D:Histogram of the proliferation of MCMEC. n=3; E:Microscopic images of angiogenesis in MCMEC; F:Histogram of the angiogenesis of MCMEC. MCMEC:Mouse coronary microvascular endothelial cells; SXBXP:Shexiang Baoxin Pills; VEGF:Vascular endothelial growth factor. a:P<0.05,b:P<0.01,c:P<0.01,compared with the normoxia control cells
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