Article(id=1304414718043648992, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304414700964443026, articleNumber=null, orderNo=null, doi=10.7501/j.issn.0253-2670.2026.04.016, pmid=null, cstr=null, oa=null, hot=0, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1760284800000, receivedDateStr=2025-10-13, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1788926303634, onlineDateStr=2026-09-09, pubDate=null, pubDateStr=null, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1788926303634, onlineIssueDateStr=2026-09-09, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1788926303634, creator=13701087609, updateTime=1788926303634, updator=13701087609, issue=Issue{id=1304414700964443026, tenantId=1146029695717560320, journalId=1302319053441957962, year='2026', volume='57', issue='4', pageStart='1209', pageEnd='1596', issueExtLink='null', onlineDate='null', pubDate='1772208000000', pubDateStr='2026-02-28', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1788926299563, creator='13701087609', updateTime=1788926573099, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1304415848316297970, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304414700964443026, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1304415848316297971, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304414700964443026, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1377, endPage=1390, ext={EN=ArticleExt(id=1304414718484050914, articleId=1304414718043648992, tenantId=1146029695717560320, journalId=1302319053441957962, language=EN, title=Effect of Shenfu Injection on tubulin post-translational modifications in rats with chronic heart failure of heart-yang deficiency syndrome based on UHPLC-MS and in vivo, in vitro experiments, columnId=null, journalTitle=Chinese Traditional and Herbal Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=Objective To screen the core active components of Shenfu Injection (参附注射液, SFI) using UHPLC-MS and molecular docking techniques, and to verify the effects of SFI on expressions of post-translational modifications of tubulin in chronic heart failure of heart-yang deficiency syndrome through in vivo and in vitro experiments. Methods UHPLC-MS was applied to identify the main components of SFI, and molecular docking was performed to analyze their interactions with tubulin-related targets. SD rats were randomly divided into control group, model group, colchicine (0.1 mg/kg) group, SFI low- and high-dose (3, 6 mL/kg) groups, with eight rats in each group. The CHF heart-yang deficiency model was replicated using sc isoproterenol, and drug intervention was given for two weeks. Echocardiography was used to detect cardiac function. ELISA was used to detect N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in serum. Hematoxylin-eosin (HE) staining was used to detect pathological changes in myocardial tissue. Immunofluorescence was used to detect the expressions of acetyl α-tubulin, polyglut α-tubulin and detyr α-tubulin in myocardial tissue. Immunohistochemistry was used to detect the expressions of tubulin tyrosine ligase (TTL) and histone deacetylase 6 (HDAC6) in myocardial tissue. H9c2 cardiomyocytes were treated with isoproterenol to establish a cell injury model, and after intervention with SFI, the level of microtubule protein modification was detected. Results A total of 12 main active ingredients in SFI were obtained through UHPLC-MS screening, and molecular docking results showed strong binding affinity with tubulin and modification related proteins. The animal experiment results showed that compared with model group, SFI could significantly improve cardiac function of rats (P < 0.01), reduce the level of NT-proBNP in serum (P < 0.01), alleviate the degree of myocardial interstitial fibrosis, reduce the expressions of microtubule protein α-tubulin and microtubule density in myocardial tissue (P < 0.05, 0.01), reduce the expressions of microtubule protein tyrosine and glutamate, increase acetylation expression, down-regulate HDAC6 positive expression (P < 0.01), and up-regulate TTL positive expression (P < 0.01). The results of cell experiments were consistent with animal experiments, further verifying that SFI could improve post-translational modifications of microtubule proteins. Conclusion SFI could effectively reduce the levels of tyrosinization and glutamatzation of microtubules, increase acetylation levels, correct the imbalance of post-translational modifications of microtubules, thereby improving the abnormal microtubule network in cardiac myocytes of rats with CHF heart-yang deficiency, enhancing microtubule stability and improving heart function. This provides experimental evidence for the molecular mechanism of SFI treatment for CHF heart-yang deficiency., authors=LI Lin, YE Jiahao, ZHAO Zhenyu, LI Weijun, HU Zhixi, authorsList=LI Lin, YE Jiahao, ZHAO Zhenyu, LI Weijun, HU Zhixi, authorCompany=null, correspAuthors=null, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, 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=1304414718421136353, articleId=1304414718043648992, tenantId=1146029695717560320, journalId=1302319053441957962, language=CN, title=基于UHPLC-MS技术及体内外实验探讨参附注射液对慢性心力衰竭心阳虚证大鼠微管蛋白翻译后修饰表达的影响, columnId=1304140191707456168, journalTitle=中草药, columnName=药理与临床, runingTitle=null, highlight=null, articleAbstract=目的 通过UHPLC-MS及分子对接技术筛选参附注射液(Shenfu Injection,SFI)核心有效成分,并通过体内外实验验证SFI对慢性心力衰竭(chronic heart failure,CHF)心阳虚证大鼠微管蛋白翻译后修饰表达的影响。方法 应用UHPLC-MS鉴定SFI的主要成分,并对其与微管蛋白相关靶点进行分子对接。SD大鼠随机分为对照组、模型组、秋水仙碱(0.1 mg/kg)组和SFI低、高剂量(3、6 mL/kg)组,每组8只,采用sc异丙肾上腺素复制CHF心阳虚证模型,给予药物干预2周。采用超声心动图检测心功能;ELISA检测血清N末端B型利钠肽原(N-terminal pro-B-type natriuretic peptide,NT-proBNP)水平;苏木素-伊红(hematoxylin-eosin,HE)染色检测心肌组织病理变化;免疫荧光检测心肌组织微管蛋白乙酰化(acetylα-tubulin)、微管蛋白谷氨酸化(polyglut α-tubulin)和微管蛋白去酪氨酸化(detyr α-tubulin)表达;免疫组化检测心肌组织微管蛋白酪氨酸连接酶(tubulin tyrosine ligase,TTL)和组蛋白去乙酰化酶6(histone deacetylase 6,HDAC6)表达。以异丙肾上腺素处理H9c2心肌细胞建立细胞损伤模型,给予SFI干预后,检测微管蛋白修饰水平。结果 UHPLC-MS筛选获得SFI中12种主要有效成分,分子对接结果显示其与tubulin及修饰相关蛋白结合力较强。动物实验结果显示,与模型组比较,SFI能显著改善大鼠心功能(P<0.01),降低血清中NT-proBNP水平(P<0.01),减轻心肌间质纤维化程度,降低心肌组织微管蛋白α-tubulin表达及微管密度(P<0.05、0.01),减少微管蛋白去酪氨酸化和谷氨酸化表达,增加乙酰化表达,下调HDAC6阳性表达(P<0.01),上调TTL阳性表达(P<0.01)。细胞实验结果与动物实验一致,进一步验证SFI能够改善微管蛋白翻译后修饰异常。结论 SFI能够有效降低微管蛋白去酪氨酸化、谷氨酸化水平,提高乙酰化水平,纠正微管蛋白翻译后修饰失衡,从而改善CHF心阳虚证大鼠心肌细胞微管网络异常,增强微管稳定性并改善心功能,为SFI治疗CHF心阳虚证的分子机制提供实验依据。, authors=李琳1, 叶嘉豪1, 赵震宇1, 李伟军1, 胡志希2, authorsList=李琳, 叶嘉豪, 赵震宇, 李伟军, 胡志希, authorCompany=1 湖南中医药大学, 湖南长沙 410208;
2 湖南中医药大学中医诊断研究所, 湖南长沙 410208, correspAuthors=胡志希, authorNote=李琳: 李琳(1988—),女,博士,副教授,研究方向为心血管疾病证本质与诊治规律。E-mail:lilin@hnucm.edu.cn 叶嘉豪: 叶嘉豪(1996—),男,博士研究生,研究方向为心血管疾病证本质与诊治规律。E-mail:1062940906@qq.com, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=Eu+SnKxo6O2SzwSm7NJ0hw==, pdfFileSize=2148291, 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=国家自然科学基金资助项目 (82305092); 国家自然科学基金资助项目 (82574922); 湖南中医药大学杏林英才支持计划 (2025); 湖南省科技创新计划资助 (2024RC3199); 湖南中医药大学优秀青年项目 (Z2023XJYQ03))}, authors=[Author(id=1307431811047510638, tenantId=1146029695717560320, journalId=null, articleId=1304414718043648992, orderNo=null, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, 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基于UHPLC-MS技术及体内外实验探讨参附注射液对慢性心力衰竭心阳虚证大鼠微管蛋白翻译后修饰表达的影响
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李琳, 叶嘉豪, 赵震宇, 李伟军, 胡志希
中草药 | 药理与临床 2026,57(4): 1377-1390
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中草药 |药理与临床 2026 , 57 (4) : 1377 -1390
基于UHPLC-MS技术及体内外实验探讨参附注射液对慢性心力衰竭心阳虚证大鼠微管蛋白翻译后修饰表达的影响
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李琳, 叶嘉豪, 赵震宇, 李伟军, 胡志希
作者信息
通讯作者:
胡志希
作者简介:
李琳: 李琳(1988—),女,博士,副教授,研究方向为心血管疾病证本质与诊治规律。E-mail:lilin@hnucm.edu.cn 叶嘉豪: 叶嘉豪(1996—),男,博士研究生,研究方向为心血管疾病证本质与诊治规律。E-mail:1062940906@qq.com
Effect of Shenfu Injection on tubulin post-translational modifications in rats with chronic heart failure of heart-yang deficiency syndrome based on UHPLC-MS and in vivo, in vitro experiments
LI Lin, YE Jiahao, ZHAO Zhenyu, LI Weijun, HU Zhixi
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doi: 10.7501/j.issn.0253-2670.2026.04.016
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目的 通过UHPLC-MS及分子对接技术筛选参附注射液(Shenfu Injection,SFI)核心有效成分,并通过体内外实验验证SFI对慢性心力衰竭(chronic heart failure,CHF)心阳虚证大鼠微管蛋白翻译后修饰表达的影响。方法 应用UHPLC-MS鉴定SFI的主要成分,并对其与微管蛋白相关靶点进行分子对接。SD大鼠随机分为对照组、模型组、秋水仙碱(0.1 mg/kg)组和SFI低、高剂量(3、6 mL/kg)组,每组8只,采用sc异丙肾上腺素复制CHF心阳虚证模型,给予药物干预2周。采用超声心动图检测心功能;ELISA检测血清N末端B型利钠肽原(N-terminal pro-B-type natriuretic peptide,NT-proBNP)水平;苏木素-伊红(hematoxylin-eosin,HE)染色检测心肌组织病理变化;免疫荧光检测心肌组织微管蛋白乙酰化(acetylα-tubulin)、微管蛋白谷氨酸化(polyglut α-tubulin)和微管蛋白去酪氨酸化(detyr α-tubulin)表达;免疫组化检测心肌组织微管蛋白酪氨酸连接酶(tubulin tyrosine ligase,TTL)和组蛋白去乙酰化酶6(histone deacetylase 6,HDAC6)表达。以异丙肾上腺素处理H9c2心肌细胞建立细胞损伤模型,给予SFI干预后,检测微管蛋白修饰水平。结果 UHPLC-MS筛选获得SFI中12种主要有效成分,分子对接结果显示其与tubulin及修饰相关蛋白结合力较强。动物实验结果显示,与模型组比较,SFI能显著改善大鼠心功能(P<0.01),降低血清中NT-proBNP水平(P<0.01),减轻心肌间质纤维化程度,降低心肌组织微管蛋白α-tubulin表达及微管密度(P<0.05、0.01),减少微管蛋白去酪氨酸化和谷氨酸化表达,增加乙酰化表达,下调HDAC6阳性表达(P<0.01),上调TTL阳性表达(P<0.01)。细胞实验结果与动物实验一致,进一步验证SFI能够改善微管蛋白翻译后修饰异常。结论 SFI能够有效降低微管蛋白去酪氨酸化、谷氨酸化水平,提高乙酰化水平,纠正微管蛋白翻译后修饰失衡,从而改善CHF心阳虚证大鼠心肌细胞微管网络异常,增强微管稳定性并改善心功能,为SFI治疗CHF心阳虚证的分子机制提供实验依据。
参附注射液  /  慢性心力衰竭  /  微管蛋白  /  去酪氨酸化  /  谷氨酸化  /  乙酰化
Objective To screen the core active components of Shenfu Injection (参附注射液, SFI) using UHPLC-MS and molecular docking techniques, and to verify the effects of SFI on expressions of post-translational modifications of tubulin in chronic heart failure of heart-yang deficiency syndrome through in vivo and in vitro experiments. Methods UHPLC-MS was applied to identify the main components of SFI, and molecular docking was performed to analyze their interactions with tubulin-related targets. SD rats were randomly divided into control group, model group, colchicine (0.1 mg/kg) group, SFI low- and high-dose (3, 6 mL/kg) groups, with eight rats in each group. The CHF heart-yang deficiency model was replicated using sc isoproterenol, and drug intervention was given for two weeks. Echocardiography was used to detect cardiac function. ELISA was used to detect N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in serum. Hematoxylin-eosin (HE) staining was used to detect pathological changes in myocardial tissue. Immunofluorescence was used to detect the expressions of acetyl α-tubulin, polyglut α-tubulin and detyr α-tubulin in myocardial tissue. Immunohistochemistry was used to detect the expressions of tubulin tyrosine ligase (TTL) and histone deacetylase 6 (HDAC6) in myocardial tissue. H9c2 cardiomyocytes were treated with isoproterenol to establish a cell injury model, and after intervention with SFI, the level of microtubule protein modification was detected. Results A total of 12 main active ingredients in SFI were obtained through UHPLC-MS screening, and molecular docking results showed strong binding affinity with tubulin and modification related proteins. The animal experiment results showed that compared with model group, SFI could significantly improve cardiac function of rats (P < 0.01), reduce the level of NT-proBNP in serum (P < 0.01), alleviate the degree of myocardial interstitial fibrosis, reduce the expressions of microtubule protein α-tubulin and microtubule density in myocardial tissue (P < 0.05, 0.01), reduce the expressions of microtubule protein tyrosine and glutamate, increase acetylation expression, down-regulate HDAC6 positive expression (P < 0.01), and up-regulate TTL positive expression (P < 0.01). The results of cell experiments were consistent with animal experiments, further verifying that SFI could improve post-translational modifications of microtubule proteins. Conclusion SFI could effectively reduce the levels of tyrosinization and glutamatzation of microtubules, increase acetylation levels, correct the imbalance of post-translational modifications of microtubules, thereby improving the abnormal microtubule network in cardiac myocytes of rats with CHF heart-yang deficiency, enhancing microtubule stability and improving heart function. This provides experimental evidence for the molecular mechanism of SFI treatment for CHF heart-yang deficiency.
Shenfu Injection  /  chronic heart failure  /  tubulin  /  detyrosination  /  polyglutamylation  /  acetylation
李琳, 叶嘉豪, 赵震宇, 李伟军, 胡志希. 基于UHPLC-MS技术及体内外实验探讨参附注射液对慢性心力衰竭心阳虚证大鼠微管蛋白翻译后修饰表达的影响. 中草药, 2026 , 57 (4) : 1377 -1390 . DOI: 10.7501/j.issn.0253-2670.2026.04.016
LI Lin, YE Jiahao, ZHAO Zhenyu, LI Weijun, HU Zhixi. Effect of Shenfu Injection on tubulin post-translational modifications in rats with chronic heart failure of heart-yang deficiency syndrome based on UHPLC-MS and in vivo, in vitro experiments[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (4) : 1377 -1390 . DOI: 10.7501/j.issn.0253-2670.2026.04.016

    国家自然科学基金资助项目 (82305092); 国家自然科学基金资助项目 (82574922); 湖南中医药大学杏林英才支持计划 (2025); 湖南省科技创新计划资助 (2024RC3199); 湖南中医药大学优秀青年项目 (Z2023XJYQ03)

参考文献 引证文献
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许顶立, 宋霖.《中国心力衰竭诊断和治疗指南2024》解读[J]. 临床心血管病杂志, 2024, 40(6): 437-439.
Caporizzo M A, Prosser B L. The microtubule cytoskeleton in cardiac mechanics and heart failure [J]. Nat Rev Cardiol, 2022, 19(6): 364-378.
Liu C, Chen Y W, Xie Y, et al. Tubulin post-translational modifications: Potential therapeutic approaches to heart failure [J]. Front Cell Dev Biol, 2022, 10: 872058.
McKenna E D, Sarbanes S L, Cummings S W, et al. The tubulin code, from molecules to health and disease [J]. Annu Rev Cell Dev Biol, 2023, 39: 331-361.
Requena S, Sánchez-Madrid F, Martín-Cófreces N B. Post-translational modifications and stabilization of microtubules regulate transport of viral factors during infections [J]. Biochem Soc Trans, 2021, 49(4): 1735-1748.
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2026年第57卷第4期
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doi: 10.7501/j.issn.0253-2670.2026.04.016
  • 接收时间:2025-10-13
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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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