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The expression of oxidative stress genes related to myocardial ischemia reperfusion injury in patients with ST-elevation myocardial infarction

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World Journal of Emergency Medicine 2022年第2期13卷 106-113页

作者： Qian-lin Gu Peng Jiang Hui-fen Ruan Hao Tang Yang-bing Liang Zhong-fu Ma Hong Zhan Emergency Department the First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510000China Huangpu District Emergency Department the First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510000China

BACKGROUND:We aimed to investigate the gene expression of myocardial ischemia/reperfusion injury(MIRI)in patients with acute ST-elevation myocardial infarction(STEMI)using stress and toxicity pathway gene chip technology and try to determine the underlying mechanism.METHODS:The mononuclear cells were separated by ficoll centrifugation,and plasma total antioxidant capacity(T-AOC)was determined by the ferric reducing ability of plasma(FRAP)assay.The expression of toxic oxidative stress genes was determined and verified by oligo gene chip and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,gene ontology(GO)enrichment analysis was performed on DAVID website to analyze the potential mechanism further.RESULTS:The total numbers of white blood cells(WBC)and neutrophils(N)in the peripheral blood of STEMI patients(the AMI group)were significantly higher than those in the control group(WBC:11.67±4.85×10^(9)/L vs.6.41±0.72×10^(9)/L,Pmyocardial band(CK-MB)on the first day(Y=8.945+0.018X,Preperfusion injury.MIRI was regulated by various genes,including o

关键词： Acute myocardial infarction myocardial ischemia/reperfusion injury Oxidative stress TNFSF6 CYP1A1 Unfolded protein response

Potential relationship between autophagy and ferroptosis in myocardial ischemia/reperfusion injury

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Genes & Diseases 2023年第6期10卷 2285-2295页

作者： Yu Yang Xianhe Lin Cardiology Department The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China Anhui Medical University HefeiAnhui 230032China

Autophagy is an evolutionarily conserved process involved in the degradation of long-lived proteins and excessive or dysfunctional organelles. As a pivotal cellular response, autophagy has been extensively studied and is known to be involved in various diseases. Ferroptosis is a recently discovered form of regulated cell death characterized by iron overload, leading to the accumulation of lethal levels of lipid hydroperoxides. Recently, an increasing number of studies have revealed a link between autophagy and ferroptosis. myocardial ischemia/reperfusion injury (MIRI) is an urgent dilemma after myocardial infarction recanalization, which is regulated by several cell death pathways, including autophagy and ferroptosis. However, the potential relationship between autophagy and ferroptosis in MIRI remains unexplored. In this study, we briefly review the mechanisms of autophagy and ferroptosis, including their roles in MIRI. Moreover, we provide an overview of the potential crosstalk in MIRI. Clarifying the relationship between different cell death pathways may provide new ideas for the treatment of MIRI in the future.

关键词： Autophagy Ferroptosis Iron overload myocardial ischemia/reperfusion injury Relationship

Progress in protective effect and mechanism of 6-gingerol on myocardial ischemia/reperfusion injury

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中国药理学与毒理学杂志 2021年第10期35卷 769-770页

作者： MA Yun-feng PAN Fei-bing ZHANG Dan-shen JING Yong-shuai College of Chemistry and Pharmaceutical Engineering Hebei University of Science and TechnologyShijiazhuang 050018China Huachuang Institute of Areca Research-Hainan Haikou 570125China

The morbidity and mortality of cardiovascular diseases are very high,which has attracted more and more attention all over the world.Common treatment methods for clinical treatment of acute myocardial infarction include direct percutaneous coronary intervention and coronary artery bypass grafting,which can quickly restore blocked coronary blood flow and reduce the infarct size.However,the inevitable ischemia/reperfusion injury will occur during the recovery of coronary blood flow,its pathological mechanism is complicated,and the Western medicine countermeasures are very limited.Among the current drugs for the treatment of cardiovascular diseases,traditional Chinese medicine has become a research hotspot due to its multiple targets,safety,and low side effects.Ginger is the fresh rhizome of Zingiber officinale Rosc.,a perennial herbaceous plant in the ginger family.It is a dual-purpose resource of medicine and food.Ginger has the functions of relieving the appearance and dispelling cold,warming up and relieving vomiting,resolving phlegm and relieving cough,and relieving fish and crab poison.The chemical components of ginger mainly include volatile oil,gingerol,diphenylheptane,etc..Among them,6-gingerol,as the main active component of gingerols,has obvious pharmacological effects in myocardial protection,anti-oxidation,anti-inflammatory,etc..Studies have shown that 6-gingerol protects myocardium mainly through anti-oxidative stress,anti-inflammatory,inhibiting cell apoptosis,and preventing calcium influx.①Anti-oxidative stress:oxidative stress is a state where oxidation and anti-oxidation in the body are out of balance,and it is also an important factor leading to myocardial damage.Many studies have confirmed that 6-gingerol has an antioxidant effect,and it is considered a natural antioxidant.6-gingerol can significantly reduce the degree of oxidative stress and the level of reactive oxygen species caused by cardiomyocyte damage,and has a significant cardioprotective effect.②Anti-inflammatory:inflammation can cause s

关键词： 6-gingerol myocardial ischemia/reperfusion injury

Mechanisms and therapeutic advances of myocardial ischemia-reperfusion injury

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South China Journal of Cardiology 2022年第1期23卷 14-18,38页

作者：张萌高山李丹阳饶宏宇 Jiamusi University Heilongjiang 154000China The First Affiliated Hospital of Jiamusi University Heilongjiang 154002China

Background The most effective treatment for Acute myocardial infarction(AMI)is timely and effective reperfusion therapy;however,the process of reperfusion therapy can worsen the myocardial damage.This pathological process is known as myocardial ischemia-reperfusion injury(I/R).But,the mechanism of I/R is not fully understood and there is no available effective treatment for I/R.This article will review the mechanisms of occurrence and treatments currently found for I/R.

关键词： myocardial ischemia/reperfusion injury acute myocardial infarction therapeutic targets

The protective effect of ginsenoside Rb1 pre-treatment on myocardial ischemia/reperfusion injury in Sprague-Dawley rats

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South China Journal of Cardiology 2020年第1期21卷 53-59,66页

作者： FANG Pin-hao LI Chang-yan YANG Jia-ni MENG Wen-ting OU Ding-qin Departments of Bioengineering Kunming Medical University Graduate school of Kunming Medical University Kunming 650500YunnanChina

Background myocardial ischemia/reperfusion injury(MI/RI)during myocardial infarction worsens outcomes. It has been proved that ginsenoside Rb1 has a great impact on ischemia/reperfusion(I/R)injury. The aim of this study is to explore the protective effect of the pretreatment with ginsenoside Rb1 on MI/RI and investigate the underlying mechanisms about the preventive action. Methods A total of 27 healthy adult Sprague-Dawley(SD)rats were randomly divided into 3 groups(n=9 per group):A sham-operated group(Sham n=9);an ischemia 40 min/reperfusion 2 h(I/R n=9)of the cardiac muscle group;Rb1-treated group was divided into 3 subgroups(Rb1 10 mg/kg,20 mg/kg,40 mg/kg,n=3). Ginsenosides Rb1 at different concentrations were injected intraperitoneally for 3 days continuously before ligation. A model of MI/RI was constructed by ligation of the left coronary artery anterior descending branch in rats. myocardial infarction area after I/R was measured bytriphenyltetrazolium chloride(TTC)staining of myocardial tissue. Hematoxylin and eosin(HE)staining and electrocardiogram indication were used to observe myocardial cell injury and ischemia,respectively. The expression of caspase-8 protein was observed by immunohistochemistry staining. Results The pretreatment of 40 mg/kg dose of ginsenoside Rb1 could decrease the expression of caspase-8 protein caused by I/R and the apoptosis of myocardial cells,improve myocardial ischemia,reduce the area of myocardial infarction and ameliorate MI/RI.Conclusions These results demonstrate that ginsenoside Rb1 has a significant protective effect on MI/RI through attenuating the apoptosis of myocardial cells and improving myocardial ischemia at appropriate dose,which provides new insights into the potential therapy of MI/RI.

关键词： myocardial ischemia/reperfusion injury ginsenoside Rb1 caspase-8 protein TTC staining HE staining

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Myeloperoxidase Aggravates myocardial Vulnerability to ischemia/reperfusion injury via Disruption of the Nitric Oxide-cGMP Pathway in Rats with Hypercholesterolemia

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Myeloperoxidase Aggravates Myocardial Vulnerability to Ische...

2019年中国生理学会心血管生理学术研讨会

作者： Ye Wu Huirong Liu Department of Physiology and Pathophysiology School of Basic Medical SciencesCapital Medical University Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Disease Capital Medical University

Aims:Hypercholesterolemia(HC) and inflammatory reaction are known to increase myocardial vulnerability to myocardial ischemia/reperfusion(MI/R) injury;however,the underlying mechanisms are not fully understood.The present study was designed to determine whether myeloperoxidase(MPO),an inflammatory cytokine expressed in cardiomyocytes following MI/R injury,exacerbated myocardial vulnerability to MI/R injury by interfering with the protective function of nitric oxide(NO) in HC rats.Methods:Male Wistar rats were fed either a normal or a high-cholesterol diet for 10 weeks,treated with vehicle or MPO inhibitor(ABAH,25.0 mg/kg/d for the last week),and subjected to MI/R(30 min/3 h or 24 h).MPO activity and distribution,cardiac function,serum LDH and CK level,myocardial infarct size,cardiomyocyte apoptosis,cardiac caspase-3 activity,NOx,nitrotyrosine(NT) level,iNOS expression,and cGMP content were assessed.Results:Compared with rats on a normal diet,MPO activity in MI/R hearts was significantly increased(1.33-fold;P myocardial cell apoptosis,MI/R injury,reduced NOx,NT,and iNOS,and increased cGMP.In addition,a scavenger of peroxynitrite(FeTMPyP) or iNOS inhibitor(1400 W) partially reversed MI/R injury in HC rats by lowering NT expression and MPO activity and raising the level of cGMP.Conclusion:Our results demonstrated that HC increased t

关键词： Myeloperoxidase hypercholesterolemia myocardial ischemia/reperfusion injury myocardial vulnerability nitric oxide

Cardioprotective effects and mechanism of Radix salviae miltiorrhizae and Lignum dalbergiae odoriferae on rat myocardial ischemia/reperfusion injury

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Cardioprotective effects and mechanism of Radix salviae milt...

中国药学会第十三届青年药学科研成果交流会

作者： Fei Mu JiaLin Duan HaiXu Bian Ying Yin YanRong Zhu Guo Wei Yue Guan YanHua Wang Chao Guo AiDong Wen Yong Yang MiaoMiao Xi Department of Pharmacy Xijing HospitalFourth Military Medical University Department of Pharmacy Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital

Objective Radix salviae miltiorrhizae（SM） and Lignum dalbergiae odoriferae（DO） are both traditional Chinese medicinal herbs for the treatment of ischemic heart disease and other cardiovascular diseases,but few of literature is about the systematic studies.Sprague-Dawley rats were pretreated with SM,aqueous extract of DO（DOA） and volatile oil of DO（DOO）,either as monotherapy or in combination for 7 days,then subjected to 30 min of ischemia followed by 180 min of reperfusion.Traditional pharmacodynamic evaluation and metabonomics based on gas chromatography/time-of-flight mass spectrometry（GC/TOF-MS） were used to identify the therapeutic effect of these traditional Chinese medicines.The results showed that SM,DOA and DOO ameliorated cardiac function respectively,and this effect was further strengthened by their combinations.Among all combinations,SM+DOO showed predominant potential（P＜0.01） to improve electrocardiogram and heart rate,reduce heart weight index and myocardial infarct size,decrease the levels of CK-MB and LDH.Moreover,metabonomics-based findings such as the principal component analysis（PCA） and partial least squares discriminant analysis（PLS-DA） score plot of metabolic state in rat serum correlated well to the preceding results,confirming that SM+DOO exerted synergistic therapeutic efficacies to exhibit better effect on MI/R injury rats compared with other pretreatment groups.Furthermore,the maximum effective point of SM+DOO was 30 min and the minimum effective point was 180 min.In addition,SM+DOO group markedly（P＜0.01） reduced the number of TUNEL-positive cells,the levels of TNF-α,IL-6 and MDA,while increased the activity of SOD both in serum and tissue.These results indicated that SM+DOO have combined effects that are highly effective than single pretreatment against MI/R injury rats.This effect might be achieved partly through anti-apoptosis,anti-oxidant and anti-inflammatory.Thus SM+DOO might be an effective and promising medicine for both prophylaxis and treatment of ischemic heart disease.

关键词： myocardial ischemia/reperfusion injury Radix salviae miltiorrhizae Lignum dalbergiae odoriferae The maximum and minimum effective points Cardioprotection Metabonomics

The serum metabolomic study of intervention effects of the traditional Chinese medicine Radix salviae miltiorrhizae and Lignum dalbergiae odoriferae in the treatment of myocardial ischemia/reperfusion injury in rats

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The serum metabolomic study of intervention effects of the t...

2016年中国药学大会暨第十六届中国药师周

作者： FEI MU JIALIN DUAN HAIXU BIAN RUI LIN MEINA ZHAO AIDONG WEN YONG YANG MIAOMIAO XI Department of Pharmacy Xijing HospitalFourth Military Medical University Department of Pharmacy Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital

. Radix salviae miltiorrhizae（SM） and Lignum dalbergiae odoriferae（DO） are both traditional Chinese medicinal herbs for the treatment of ischemic heart disease and other cardiovascular diseases, but few of literature is about the systematic studies. Sprague-Dawley rats were pretreated with SM, aqueous extract of DO（DOA） and volatile oil of DO（DOO）, either as monotherapy or in combination for 7 days, then subjected to 30 min of ischemia followed by 180 min of reperfusion. Traditional pharmacodynamic evaluation and metabonomics based on gas chromatography/time-of-flight mass spectrometry（GC/TOF-MS） were used to identify the therapeutic effect of these traditional Chinese medicines. The results showed that SM, DOA and DOO ameliorated cardiac function respectively, and this effect was further strengthened by their combinations. Among all combinations, SM+DOO showed predominant potential（P＜0.01） to improve electrocardiogram and heart rate, reduce heart weight index and myocardial infarct size, decrease the levels of CK-MB and LDH. Moreover, metabonomics-based findings such as the principal component analysis（PCA） and partial least squares discriminant analysis（PLS-DA） score plot of metabolic state in rat serum correlated well to the preceding results, confirming that SM+DOO exerted synergistic therapeutic efficacies to exhibit better effect on MI/R injury rats compared with other pretreatment groups. Furthermore, the maximum effective point of SM+DOO was 30 min and the minimum effective point was 180 min. In addition, SM+DOO group markedly（P＜0.01） reduced the number of TUNEL-positive cells, the levels of TNF-α, IL-6 and MDA, while increased the activity of SOD both in serum and tissue. These results indicated that SM+DOO have combined effects that are highly effective than single pretreatment against MI/R injury rats. This effect might be achieved partly through anti-apoptosis, anti-oxidant and anti-inflammatory. Thus SM+DOO might be an effective and promising medicine for both prophylaxis and treatment of ischemic he

关键词： myocardial ischemia/reperfusion injury Radix salviae miltiorrhizae Lignum dalbergiae odoriferae The maximum and minimum effective points Cardioprotection Metabonomics

Cardioprotective effects of Salvia miltiorrhiza Bunge and Lignum dalbergiae odoriferae on rat myocardial ischemia/reperfusion injury

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Cardioprotective effects of Salvia miltiorrhiza Bunge and Li...

2015年中国药学大会暨第十五届中国药师周

作者： MU Fei DUAN Jia-lin BIAN Hai-xu YIN Ying ZHU Yan-rong WEI guo GUAN Yue WANG Yan-hua GUO Chao WEN Ai-dong XI Miao-miao Department of Pharmacy Xijing Hospital Fourth Military Medical University

Aim: Salvia miltiorrhiza Bunge（SM） and lignum dalbergiae odoriferae（DO） are both traditional Chinese medicine that have cardioprotective effects. Here, we further examined the combined effects of SM and DO on rat myocardial ischemia/reperfusion injury. The possible mechanism of SM and DO also were elucidated. Material and Methods: DO was divided into aqueous extract of lignum dalbergiae odoriferae（DOW） and lignum dalbergiae odoriferae oil（DOO）. Sprague-Dawley rats were randomized to seven groups: sham group, model group, treatment groups including SM（10 g/kg）, DOW（5 g/kg）, DOO（0.5 ml/kg）, SM+DOW（10 g/kg+5 g/kg）, SM+DOO（10 g/kg+0.5 ml/kg）. Rats were pretreated with homologous drug for 7 days and then subjected to 30 min of ischemia followed by 180 min of reperfusion. Electrocardiogram（ECG） and heart rate were monitored and recorded continuously. At the end of reperfusion, blood samples were collected to determine the serum levels of creatine kinase-MB（CK-MB） and lactate dehydrogenase（LDH）. Hearts were harvested to assess heart-body rate, infarct size and histopathological changes as well. Maximum and minimum effective points were determined by measuring indicators associate with myocardial injury at different time-points of reperfusion（5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min）. The potential therapeutic mechanism of SM and SM+DOO were carried out by detecting superoxide dismutase（SOD）,malondialdehyde（MDA）, tumor necrosis factor-alpha（TNF-alpha） and interleukin 6（IL-6）. Results: The results showed SM and DO can ameliorate cardiac function respectively, and this cardioprotective effect was further strengthened by their combinations. Among all the combinations, SM+DOO showed predominant potential to improve ECG and heart rate, reduce heart-body rate（28.5% ±1.4%, P＜0.01 vs model）and myocardial infarct size（20.96%±1.61%,P＜0.01 vs model, P＜0.05 vs SM）, attenuate histopathological damage, decrease the levels of CK-MB and LDH（P＜0.01 vs model, P＜0.05 vs SM）. The maximum effective points of SM and SM+DOO were

关键词： myocardial ischemia/reperfusion injury Salvia miltiorrhiza Bunge Lignum dalbergiae odoriferae the maximum and minimum effective points anti-oxidant anti-inflammatory